The use of energy drinks and capsules have recently been shown to be the most popular supplement besides multivitamins in the American adolescent and young adult populations, as more than 30% of American adolescents self-admit to using thermogenic supplements on a regular basis 1. The primary reason for use of these supplements is thought to be related to their desire to reduce or control body fat 123. A number of herbal ingredients have been proposed as being effective agents in increasing energy expenditure and reducing body fat 4. Although studies examining the thermogenic effect (i.e. increase in caloric expenditure) from high-energy supplements are limited, several recent investigations have suggested that the combination of thermogenic agents in a supplement may be more effective in increasing the thermogenic effect than a single herbal ingredient 56.

Caffeine has been shown to be an effective supplement in enhancing lipolysis, fat oxidation, and reducing glycogen breakdown 78, however when combined with other thermogenic agents its effectiveness appears to be magnified 56. For many years caffeine was often combined with ephedra that resulted in an enhanced metabolic response leading to greater body fat loss 910. However, as a result of the Federal Drug Administration's ban on ephedrine alkaloids in 2004 the use of alternative therapeutic means to combat obesity has been examined. Synephrine is a mild stimulant and is thought to contribute to appetite suppression, increased metabolic rate and lipolysis 11. Synephrine is thought to stimulate specific adrenergic receptors (β-3) that stimulate fat metabolism without any of the negative side effects (i.e., elevated systolic blood pressure, heart rate and thermogenic strain) generally associated with compounds that stimulate the other adrenergic receptors 12. Recent research has suggested that to maximize the effectiveness of synephrine as an effective weight loss supplement it may need to be combined with other herbal products 13. Some of these products may include yohimbine, yerba mate extract, hordenine and methyl tetradecylthioacetic acid. All of which have been shown to play a role in enhancing lipolysis and increasing energy expenditure 141516.

In addition to increasing thermogenesis many of these supplements may also contain herbal ingredients whose primary role is to enhance mood. Phenylethylamine is an example of an endogenous neuroamine that has been included in weight loss supplements. Several studies have shown that phenylethylamine can relieve depression and improve in clinical populations 1718. Much of the work on phenylethylamine was based upon research that demonstrated that a deficit in phenylethylamine can be responsible for depression 19. As a result, it has been used both clinically to treat depression, and in energy supplements to enhance mood.

Considering the high propensity in the use of these thermogenic supplements, research is warranted concerning the efficacy of these energy supplements. Thus, the purpose of this study was to examine the acute effect of a weight loss supplement containing several herbal and botanical ingredients on resting oxygen uptake, respiratory quotient, caloric expenditure, heart rate, and blood pressure in healthy and physically active individuals.

A significant difference (p = 0.01) in average energy expenditure was seen between SUP (1.28 ± 0.33 kcal·min^-1) and P (1.00 ± 0.32 kcal·min^-1) during the entire 3-hr period (see Figure 1). Significant differences in the average energy expenditure between the groups were also seen at each hour of the protocol (see Table 1).

The average hourly cardiovascular response to the study protocol is seen in Table 1. Heart rate was significantly higher during hours two and three for SUP compared to P. The average systolic blood pressure response in SUP was significantly higher at each hour compared to P. The average systolic blood pressure response for the 3-hr protocol was also significantly greater (p = 0.002) for SUP than P (see Figure 2a). No difference between the groups was seen in the diastolic blood pressure response (Table 1 and Figure 2b).

The average RQ was significantly lower for SUP than P at hours two and three (see Table 1). In addition, a trend (p = 0.06) towards a greater utilization of stored fat as an energy source, expressed as energy expenditure from fat, was also demonstrated during the 3-hr study protocol for SUP compared to P (see Figure 3).

Comparisons between groups in the average profile of mood states scores can be observed in Figure 4. No significant differences were seen in the average score for the mood states depression, anger, vigor, and fatigue. However, a significantly higher average tension and confusion score was observed during SUP compared to P.

The results of this study indicate that a weight loss supplement containing anhydrous caffeine, synephrine, tetradecylthioacetic acid, yerba mate extract, methylphenylethylamine, yohimbine, and hordenine is effective in increasing acute energy expenditure in young, healthy individuals. Ingestion of this supplement also resulted in significant elevations in heart rate and systolic blood pressure indicating a strong inotropic response to this supplement. In addition, acute ingestion of this supplement increased tension and confusion among subjects.

Comparisons between weight loss supplements need to be performed carefully considering the large variability seen in ingredients or different concentrations of ingredients. Previous research has shown that acute ingestion of caffeine, synephrine and other herbal ingredients in a coffee supplement significantly increased energy expenditure 12% among healthy, lean college students 6. In this present study, using a similar subject population the combination of anhydrous caffeine, synephrine and different herbal ingredients resulted in a 29% increase in energy expenditure. Although differences could be related to differences in concentrations of similar ingredients within each supplement, the difference between these studies is likely related to the differences in co-ingredients within the supplement.

Caffeine and herbal supplements have been shown to increase resting metabolic rate for up to three hours following ingestion 61021. These effects have been shown in supplements combining caffeine with ephedra and black tea 1021, and with caffeine combined with synephrine, garcinia cambogia and chromium polynicotinate 6. The greater energy expenditure seen in this study compared to others is likely related to the additional ingredients in this supplement that have previously been found to enhance metabolism and therefore have a synergistic effect with known thermogenic ingredients such as caffeine.

Synephrine is a mild stimulant that comes from the fruit citrus aurantium (bitter orange). It is the predominant alkaloid from this fruit, and is thought to stimulate fat metabolism 12. Hordenine is an alkaloid that occurs naturally in grains, sprouting barley and certain grasses, but it is also found in small quantities in citrus aurantium 22. When infused to horses it has been shown to increase respiratory and heart rates, however when provided orally no significant cardiorespiratory changes were seen 23. Other studies have suggested that hordinine can exert its stimulating effect by inhibiting norepinephrine uptake 15. Although human studies with hordinine are very limited, it is likely it works synergistically with synephrine to enhance the sympathetic response.

The elevated blood pressure and heart rate responses seen during the SUP treatment are similar to other studies examining weight loss supplements containing adrenergic amines 561324. Synephrine is thought to increase lipolysis and minimize the cardiovascular effect typical of adrenergic amines 12, however synephrine has also been shown to stimulate peripheral α-1 receptors resulting in vasoconstriction and elevations in blood pressure 25. Although synephrine ingested alone may not alter blood pressure, when ingested in combination with other active herbal ingredients does appear to elevate blood pressure and heart rate 56. The combination of synephrine, caffeine and hordinine used in this study appears to cause significant elevations in the cardiovascular response to supplement ingestion.

The trend towards a greater utilization of stored fat as the primary energy source, as evidenced by a lower RQ, in this study is likely related to the combination of yohimbine, yerba mate extract and tetradecylthioacetic acid. The precise concentrations of yohimbine and its metabolites in this supplement are not known, thus discussion concerning how these differences may have effected changes in fat mobilization would only be speculative. Yohimbine is a selective α-adrenoceptor antagonist that has been shown to be effective in enhancing lipid metabolism 1626. However, the extent of yohimbine's effect may have been modulated by its various metabolites within the supplement. No differences in RQ between the groups were seen in the first hour following supplementation but significant differences were seen at hours two and three. This may be reflective of differences in α-2 adrenoceptor blocking potency and half-life between the metabolites of yohimbine 27. Although yohimbine is a more potent α-adrenoceptor antagonist than its metabolites, it is metabolized more quickly.

Yerba mate extract made from the leaves of the tree Ilex paraguariensis has been shown to suppress appetite and prevent diet-induced obesity in rats 28 and humans 14. It is thought to cause weight reduction by delaying gastric emptying 14 and its effects may be enhanced by caffeine 4. Although it is proposed to have several potential health benefits besides weight loss 29, its role in elevating energy expenditure or increasing lipolysis is not well understood, and may be negligible. Tetradecylthioacetic acid has been shown to be effective in enhancing fatty acid metabolism 30.

The addition of phenylethylamine as an ingredient was thought to enhance the mood of subjects using this supplement. Phenylethylamine has been shown to produce relief of depression among a clinical population, even in those that were unresponsive to standard treatments 18. An advantage in the use of phenylethylamine is thought to be related to the beneficial mood improvements seen without producing a tolerance often associated with amphetamines 18. The mechanism of its effect appears to be related to the stimulation of dopamine release 31. This may contribute to an improved mood state and has also been shown to potentially reduce appetite 32. In addition, phenylethylamine may also stimulate lipolysis through its ability to stimulate catecholamine release and delay reuptake 33. The results of this study indicate that phenylethylamine did not affect mood, but may have contributed to the greater reliance on fat as an energy source. Considering the various ingredients within this supplement, it is possible that the greater tension and confusion seen in SUP may have been a result of the adrenergic stimulants contained in the supplement.

In conclusion the results of this study indicate that following an acute ingestion of a weight loss supplement containing anhydrous caffeine, synephrine, tetradecylthioacetic acid, yerba mate extract, methylphenylethylamine, yohimbine, and hordenine leads to a significant increase in energy expenditure in young, healthy individuals. In addition, ingestion of this supplement stimulates elevations in heart rate and blood pressure for three hours, while increasing feelings of tension and confusion. Individuals who have been diagnosed with cardiovascular disease need to be aware of the significant cardiovascular effects resulting from use of this supplement. Additional research is warranted concerning the long-term effects of consumption of this supplement, and whether such supplementation can translate into weight loss or improved body composition.

Vital Pharmaceuticals. (Davie, FL) provided funding for this project. All researchers involved independently collected, analyzed, and interpreted the results from this study and have no financial interests concerning the outcome of this investigation. Publication of these findings should not be viewed as endorsement by the investigator, The College of New Jersey or the editorial board of the Journal of International Society of Sports Nutrition.

JRH was the primary investigator, obtained grant funds for project, designed study, supervised all study recruitment, data/specimen analysis, statistical analysis and manuscript preparation. JK, NAR, and ADF were co-authors, oversaw all aspects of study including recruitment, data/specimen analysis, and manuscript preparation. SCR, and CPT were co-authors, assisting with data collection and data analysis.