A commonly used pharmacological agent, caffeine is very well-studied and extensively used; in fact, caffeine is the most widely consumed pharmacological substance in the world. The most well-described physiological effects of caffeine relate to enhanced mood, cognition, exercise performance, and weight loss associated outcomes (e.g., increased thermogenesis [Belza et al., 2009] such as increased free fatty acid release and catecholamine levels [Patwardhan et al., 1980], decreased appetite). Multiple mechanisms are associated with the ergogenic effect of caffeine including improved cognitive function, increased catecholamine secretion and associated lipolysis, enhanced Na+/K+ pump activity serving to enhance excitation contraction coupling, increased calcium mobilization, phosphodiesterase inhibition, and antagonism of adenosine receptors. While individual response to caffeine varies based on tolerance, studies have generally ranged from 3-6 mg•kg-1 body mass.

2-amino-4-methylhexane appears to provide a sympathomimetic effect in human subjects; that is, it is thought to mimic the effects of the sympathetic nervous system such as the endogenous chemicals epinephrine, norepinephrine, and dopamine. This does not indicate that it necessarily elevates these chemicals; rather, it may mimic their effects such as enhanced fatty acid mobilization from storage depots and providing a feeling of euphoria. This is the one ingredient contained within Fat Smack XR™ that is not yet supported by peer-reviewed, published clinical data; however, research pertaining to its use in human subjects is ongoing, and immense anecdotal reports exist for improved focus, mood, exercise performance, and extreme appetite suppression. The dosage of 2-amino-4-methylhexane contained within Fat Smack XR™ is based on observations in human subjects using 2-amino-4-methylhexane alone and in combination with caffeine at varying amounts, as well as pilot testing done by Purus Labs® in a variety of healthy men and women with normal blood pressure.

EGCG) is one of several catechins, and is the ester of epigallocatechin and gallic acid. EGCG is found in relatively high amounts within tea (green tea in particular), has multiple physiological properties ranging from antioxidant activity to fueling weight/fat loss (Saito et al., 2009), and is generally viewed as a candidate ingredient in the treatment of metabolic syndrome (Thielecke and Boschman, 2009). In short, the beneficial effects of green tea consumption have been reported in multiple peer reviewed manuscripts; related to weight loss, EGCG (or more specifically green tea extract) has been reported to decrease ad libitum energy intake (Belza et al., 2009), increase fat oxidation at rest (Boschman andThielecke, 2007) and during moderate-intensity exercise (Venables et al., 2008), improve insulin sensitivity and glucose tolerance (Venables et al., 2008), increase 24-hour energy expenditure (Bérubé-Parent et al., 2005), increase dietary-induced thermogenesis via inhibition of catechol-O-methyltransferase (Shixian et al., 2006)—an enzyme contributing to the degradation of catecholamines—as well as enhance weight loss (Di Pierro et al., 2009) and exercise-induced abdominal fat loss (Maki et al., 2009). An interesting finding (Henning et al., 2004) noted that the addition of ascorbic acid (vitamin C) at an amount of 30mg to a 250mL tea beverage increased the catechin digestive recovery of epicatechin (EC), epigallocatechin (EGC), EGCG, and epicatechin-gallate (ECG) when tested using an in vitro digestion simulating gastric and small intestinal conditions. These findings are the rationale for the inclusion of vitamin C to the Fat Smack XR™ ingredient profile (see below- Vitamin & Mineral Matrix).

Cissus quadrangularis (CQ) is one of the most commonly used medicinal plants in Thailand and used in traditional African and Ayurvedic medicine. As with green tea extract, CQ renders multiple physiological effects including potent antioxidant effects to minimize oxidative stress, anti-arthritis benefits, as well as anti-obesity properties. Specifically, the chemical constituents of CQ (e.g., flavonoids, phytosterols and keto-steroids) have shown promise as powerful antioxidants and demonstrated efficiency for lipase and amylase inhibition—collectively contributing to reduced oxidative stress and weight loss. At least three human studies have been conducted using this agent, all reporting beneficial effects on weight loss and associated variables. In summary, these studies found CQ alone, or in conjunction with other materials, caused statistically significant reductions in body weight, central obesity, body fat, waist size, cholesterol, and fasting blood glucose (Oben et al., 2006-2007-2008). Considering the work performed by Oben and colleagues, the results for use of CQ are very impressive, and an extremely positive attribute of the Oben work is the fact that all studies included a relatively large sample size, something that is lacking in many dietary supplement intervention studies.

Capsaicinoids are the major pungent, naturally occurring active compounds in capsicum fruits such as hot chili peppers. The most abundant forms of capsaicinoids found within hot red peppers are capsaicin (8-methyl-N-vanillyl-6-nonenamide), dihydrocapsaicin, and nordihydrocapsaicin (Thomas et al., 1998). Capsaicinoid ingestion is typically associated with intense feelings of heat. In fact, the amount of heat generated by these capsaicinoids is actually measured using Scoville Heat Units (SHU), with pure capsaicin yielding the highest measure of 15,000,000 SCU. With such a high rating, very little capsaicin in needed to provide a measureable effect, and too much may be associated with gastrointestinal upset. In terms of effects related to weight/fat loss, capsaicinoids have been reported in multiple studies to reduce ad libitum food intake, increase thermogenesis and energy expenditure, enhance lipolysis (for a review please see Bloomer et al., 2009b), and inhibit adipogenesis (Hsu and Yen, 2007). Capsaicinoids are thought to function to stimulate thermogenesis by activating the sarcoplasmic reticulum Ca+-ATP-ase (SERCA). Thermogenesis, as indicated earlier, refers to process of heat generation via the hydrolysis of ATP via SERCA. In the presence of capsaicinoids, SERCA becomes uncoupled (i.e., ATP hydrolysis occurs without the transport of calcium) leading to greater heat energy production (Mahmmoud, 2008). In terms of lipolysis, capsaicinoids are an agonist of the transient receptor potential vanilloid subfamily member 1 (TRPV1). TRPV1, via a number of steps, ultimately leads to an increased activation of the sympathetic nervous system leading to the release of epinephrine and norepinephrine from adrenal glands. These anorectic catecholamine hormones interact with hormone sensitive lipase, an enzyme involved in lipolysis and the mobilization of fatty acids from storage sites. Epidemiological data appear to support an association between the consumption of capsaicinoid containing foods and a lower incidence of obesity (Wahlqvist and Wattanapenpaiboon, 2001).

Fat Smack XR™ contains a vitamin/mineral matrix to enhance the activity of the other ingredients (Vitamin C-see above EGCG) (Henning et al., 2004), support optimal thyroid function (numerous studies can be found in support of our included vitamin/mineral matrix regarding healthy thyroid-see PubMed, Linus Pauling Institute, and the NIH Office of Dietary Supplements), and as an overall antioxidant. Several of the ingredients provided within this matrix are known to support healthy thyroid (vitamin A, selenium, iodine, iron, and zinc) which is important for the regulation of metabolic rate (energy expenditure). We are not boasting, nor did we focus on, a prolific thyroid stimulating blend to increase thyroid activity beyond normal, healthy function; but instead, we aimed to construct a cocktail that truly supports and encourages optimal thyroid function.

Piperine is an extract of black pepper and appears to function in a similar manner as capsaicinoids (binding the TRPV1 receptors) by increasing catecholamine secretion, hence thermogenesis. Piperine is often used within nutritional supplements as an aid in absorption, as it may promote rapid absorption of certain nutrients (e.g., curcumin, vitamins, amino acids) from the gastrointestinal tract (Johri, R.K. et al., 1992)( Kowado, T, et al., 1988). For these pertinent reasons, it serves as a synergist within Fat Smack XR's conglomerate.