Cissus Quadrangularis
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. As an aside, although noted using an animal model, CQ stem extract was recently reported to provide hepatoprotection by exhibiting antioxidant and insulin-sensitizing activities (Chidambaram and Venkatraman, 2010). Coupled with the human evidence provided below, CQ appears to have promise as a health-enhancing, weight/fat loss agent.
In the first study using CQ (Oben et al., 2006), 123 overweight and obese individuals (47.2% male; 52.8% female; ages 19-50) were enrolled. The 92 obese subjects were randomized into three groups; placebo, CQ formulation/no diet, and CQ formulation/diet (2100-2200 calories/day). The 31 overweight subjects formed a fourth (no diet) treatment group. All subjects received two daily doses of the CQ formulation (CQ extract, soy albumin extract, green tea extract, niacin bound chromium, selenium, vitamin B6, vitamin B12, and folic acid) or placebo and remained on a normal or calorie-controlled diet for 8 weeks. Results indicated that
statistically significant net reductions in body weight and central obesity, as well as in fasting blood glucose, total cholesterol, LDL-cholesterol, triglycerides, and C-reactive protein (a marker of systemic inflammation) were observed in subjects who received the CQ formulation, regardless of diet. HDL-cholesterol was also increased significantly. Collectively, these data indicate that CQ (in particular when combined with other ingredients as used in the present study) might be a viable candidate in a weight/fat loss product, as multiple health related effects are observed with treatment.
In a follow-up study conducted using CQ (Oben et al., 2007), a proprietary extract of CQ was compared to a proprietary formulation containing CQ on measures of weight, blood lipids, and oxidative stress (free radical mediated oxidation of large and small molecules) in a sample of overweight and obese subjects. Part one of the study investigated the
in vitro antioxidant properties of the two conditions, while part two of the study included a double-blind placebo controlled design, enrolling initially 168 overweight and obese subjects (38.7% males; 61.3% females; ages 19-54), of whom 153 completed the study. Subjects received two daily doses of either condition or a placebo and were instructed to maintain their normal levels of physical activity. Results indicated that both conditions containing CQ exhibited antioxidant properties
in vitro, as well as
in vivo, as they resulted in significant reductions in plasma thiobarbituric acid reactive substances (TBARS) and protein carbonyls. Both conditions also brought about
significant reductions in weight, body fat, total cholesterol, LDL-cholesterol, triglycerides, and fasting blood glucose levels over the intervention period, alongside an increase in both HDL-cholesterol and plasma 5-HT. Taken together, these findings indicate both weight/fat loss and cardio-protective properties of CQ supplementation.
The third study conducted using CQ involved an evaluation of the effects of two formulations, CQ-only and a CQ/Irvingia gabonensis combination, on weight loss in overweight and obese human subjects (Oben et al., 2008). The study involved a 10 week intervention period in which subjects (72 obese or overweight men and women (45.8% male; 54.2% female; ages 21-44; mean age = 29.3) were randomized using a double-blind, placebo-controlled design to three equal (n = 24) groups: placebo, CQ-only and CQ/Irvingia gabonensis combination. No major dietary or exercise changes were suggested during the study.
Body weight, body fat (using bio-electrical impedance), waist size, total plasma cholesterol, LDL cholesterol, fasting blood glucose level were taken at baseline and at 4, 8 and 10 weeks. Results indicated that compared to the placebo group, the two active groups demonstrated a
statistically significant difference on all six variables by week 10, with a greater change noted at week 10 compared to week 4 (even greater change was noted in the CQ/Irvingia gabonensis combination group). The decrease in body weight with CQ alone was approximately 19 pounds (~9%) in the 10 week intervention. While this is impressive, the most striking changes were noted in the reduction in blood cholesterol and glucose values—which admittedly, are so impressive they are almost difficult to believe (in particular for the CQ/Irvingia gabonensis combination).
Although subjects in this study were overweight or obese (BMI >25kg∙m[SUP]-2[/SUP]), many individuals planning to use a weight/fat loss agent also fall into these categories; hence, these data are highly specific to many considering using Fat Smack™. These results agree with prior work in human subjects using CQ and suggest this ingredient may prove beneficial in overall weight loss over time, while providing cardio-protective properties specifically related to a reduction in oxidative stress and an improvement in blood lipids.
Considering the work performed by Oben and colleagues, the results for use of CQ are very impressive, especially in terms of the changes in bloodborne measures. A 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. Of course, the greater sample size also increases the likelihood of obtaining statistically significant findings (due to the increase in statistical power). Further studies, by different groups of investigators, are needed to corroborate the findings of Oben and coworkers. Lastly, few adverse events were noted in the above studies using CQ (e.g., headache, lack of sleep, gas), which were similar to those reported with use of placebo.
Capsaicinoids
Capsaicinoids are the major
pungent, naturally occurring active compounds in capsicum fruits such as hot chili peppers—a fruit of the genus capsicum plant family. 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). If consuming whole hot peppers, approximately 3mg of capsaicinoids are present within 1g of dried red pepper (Yoshioka et al., 1995).
Capsaicinoid ingestion is typically associated with intense feelings of heat. In fact, the amount of heat generated by these capsaicinoids is typically 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, and enhance lipolysis (for a review please see Bloomer et al., 2009b). The lipolytic effect has been recently demonstrated using a very low dose capsaicinoid (Bloomer et al., 2010). Although the exact mechanisms are not yet fully understood, it is believed that capsaicinoids limit weight gain or may induce a weight loss via inhibiting adipogenesis, a finding noted using a cell culture study (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 catecholamine hormones interact with hormone sensitive lipase, an enzyme involved in lipolysis and the mobilization of fatty acids from storage sites. The increase in catecholamine secretion may be responsible for the reduction in ad libitum food intake noted with capsaicinoid intake—which may be due to the anorectic effects of catecholamines (Russek et al., 1987).
It is important to note, as with data pertaining to other ingredients presented within this paper, that these findings have been noted in human subjects, consuming capsaicinoids (or red peppers; and sometimes CH-19 sweet peppers or non-pungent capsinoids) in oral form. As is the case for most ingredients, while
not all studies have reported positive outcomes for the above variables, the majority of published work has noted positive effects related to at least one of the above outcome measures. Unfortunately, some manuscripts fail to report on the specifics of the ingested treatment (e.g., capsaicin or dihydrocapsaicin capsules, CH-19 sweet peppers, capsiate or dihydrocapsiate capsules, etc.) and rather state either
pepper intake or
capsule intake. Therefore, the exact dosage of capsaicinoids used is sometimes unknown. Despite this, epidemiological data appear to support an association between the consumption of capsaicinoid containing foods and a lower incidence of obesity (Wahlqvist and Wattanapenpaiboon, 2001). This finding, coupled with the specific effects noted above, qualify capsaicinoids as an integral ingredient for inclusion within Fat Smack™.
From a safety perspective, the lethal dose of capsaicinoids is estimated at 47.2mg/kg (mouse) (see
www.sciencelab.com for Material Safety Data Sheet), an amount that is significantly higher than that used in any clinical study to date. Despite this fact, it should be noted that certain individuals may experience gastric discomfort and a burning sensation with intake and may view this as an adverse reaction. While it is sometimes noted that capsaicinoids promote gastric ulcers, this is refuted in a review on the topic (Satyanarayan, 2006) with the author noting that “investigations carried out in recent years have revealed that chilli or its active principle capsaicin is not the cause for ulcer formation but a benefactor.” Nonetheless, individuals with aversions to hot and spicy foods may not tolerate capsaicinoid intake well. Additional safety information can be found in the following article (Anonymous, 1998).
Piperine
Piperine is an extract of black pepper and appears to function in a similar manner as capsaicinoids (by binding the TRPV1 receptors). Piperine is often used within nutritional supplements as an aid in absorption (at a dosage of 5mg—the same dosage as used in Fat Smack™), as it may promote rapid absorption of certain nutrients (e.g., curcumin, vitamins, amino acids) from the gastrointestinal tract. Specifically, it has been used in combination with caffeine and capsaicinoids in a recent investigation in which the authors reported an increase in energy expenditure with supplement use (Ryan et al., 2009). Beyond this,
in vitro studies have demonstrated effects ranging from enhanced antioxidant activity to protecting against oxidative damage via quenching free radicals (Srinivasan, 2007). For these purposes, piperine (which is a Generally Recognized as Safe [GRAS] ingredient) is included within Fat Smack™.
Vitamin/Mineral Mix
Fat Smack™ contains a vitamin/mineral matrix to enhance the antioxidant activity of the other ingredients (e.g., EGCG and CQ), as well as for the support of healthy thyroid function. Several of the ingredients provided within this matrix are known to support healthy thyroid (e.g., vitamin A, selenium, iodine, iron, and zinc) which is important for the regulation of metabolic rate (energy expenditure). It should be noted that while these nutrients are well-known to support healthy thyroid function, no outlandish claims are made in support of this matrix beyond this. That is, unlike some companies, PURUS LABS® is in no way making claims that this particular blend of thyroid supporting ingredients will elevate thyroid to “drug-induced” levels. This is unnecessary and potentially undesirable in a product such as Fat Smack™, which is strong enough considering the ingredient profile aside from the vitamin/mineral mix.
While certain agents are used within some nutritional supplements in an attempt to boost thyroid activity, and may be capable of doing so when studied in animal models at high dosages, little or no direct evidence is available to support their use in human subjects. Consider for example, 3,5-diiodo-L-thyronine, which has indeed been reported to have thyromimetic effects
in vivo, but is routinely delivered to
hypothyroid animals (often via IV injection) at doses from 2.5 to 10 µg/100g body weight (Moreno et al., 1998), an amount equivalent to multiple
milligrams quantities in man. While this may not seem like a high dosage, the sheer price of this material renders this ingredient impossible to include at an efficacious amount; some supplement companies choose to use small
MICROgram amounts of this ingredient within their proprietary blends. While it is possible that a much lower dosage could provide some beneficial effect, this has yet to be supported by clinical study.
Besides the above, there is no evidence related to the
long-term impact of many such agents on thyroid function. It is possible, as with many other exogenous agents administered in an attempt to boost natural hormone production, that the body may down-regulate endogenous production of thyroid hormone over time if chronically supplementing with a supposed thyroid hormone booster. Due to these issues, PURUS LABS® has simply decided not to focus specifically on attempting to boost thyroid function by using “novel,” supposed thyroid stimulators; instead, Fat Smack™ is fueled by a combination of ingredients thought to support healthy thyroid function in human subjects. Perhaps data pertaining to the use of naturally occurring agents that
stimulate thyroid function in human subjects will become available in coming years, at which time they will be systematically investigated for potential inclusion within a revised Fat Smack™. However, at this time, the data simply are not available.
SUMMARY
Fat Smack™ contains a carefully selected blend of ingredients, based on
human evidence for effect in relation to multiple aspects of weight/fat loss, and used at the research-proven dosages. While regular exercise and optimal dietary intake inclusive of frequent, macronutrient balanced and nutrient dense meals (as well as adequate water intake) should be viewed as most important in the quest for body weight/fat reduction and the reduction of cardiovascular and metabolic disease risk, use of a weight/fat loss agent such as Fat Smack™ may be an adjunct to this lifestyle plan.
As with all nutritional supplements, potential users should only use Fat Smack™ under the guidance of their personal physician. Individuals considering using Fat Smack™ should be healthy and over the age of 21. They should not have any diagnosed medical conditions or family history of medical conditions related to, but not limited to, high blood pressure, heart disease, stroke, or any other disease of cardiovascular or metabolic origin. Due to the pepper extracts used in this product, individuals with aversions to spicy foods may need to limit use of the product. Individuals subjected to anti-doping regulation by their athletic organizations should be advised that the 2-amino-4-methylhexane used within this product (and several other products currently sold on the supplement market) is currently considered a banned substance by certain athletic organizations. Individuals should review the product nutrition panel and label for information regarding the ingredients, dosing, and precautions for use. For more information on PURUS LABS® and its other performance/physique-enhancing products, please visit
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