Dietary Supplements: Focusing on Fat

“I feel fat.” It’s something many of us have bemoaned at some point. According to the Centers for Disease Control and Prevention, more of us may be saying it soon. Almost one-third of U.S. adults are not just overweight but clinically obese-a growing figure that not only threatens our figures but, more importantly, our nation’s health at large.

The average consumer is aware of the basics of weight management: that excess calories in over calories out leads to weight gain, and that physical exercise and a healthy diet are crucial. However, as Americans, our physicians, and our government look desperately for ways to cut the fat, researchers are exploring more-specific factors in the weight-management equation.

In the dietary supplements industry, companies have taken various approaches to weight management, including satiety and appetite suppression. In this article, we visit some of the ingredients targeting the breakdown or burning of fat.

The Skinny on Fat

There are two kinds of fat. Brown adipose tissue, also known as brown fat or BAT, is the good kind because researchers say it actually burns calories.

White adipose tissue, WAT or white fat, on the other hand, is far more plentiful than brown fat. It’s the fat stored for energy, and too much of it is associated with being overweight.

White fat itself exists in two forms. Subcutaneous fat is the fat beneath the skin and in the thighs and buttocks. The other type of white fat, visceral fat, is stored specifically in the peritoneal (abdominal) cavity, packed between vital organs like the stomach, liver, intestines, and kidneys. It’s excess visceral fat that’s to blame for a large abdomen, or a “beer belly.” And, according to researchers, it can be the most dangerous kind of fat.

Excess visceral fat is a key factor in metabolic syndrome. Specifically, visceral fat may be a precursor for health problems such as diabetes and cardiovascular disease by impairing glucose and lipid metabolism. As an example, excess visceral fat may slow the production of adiponectin, the hormone produced by fat tissue that regulates glucose sensitivity. As a result, a person may develop increased insulin resistance and chances of developing type 2 diabetes.

The medical community is certainly putting more emphasis on monitoring visceral fat. Researchers acknowledge that more science is needed to connect visceral fat with specific health hazards.
 

Ingredients that May Help

While no one dietary ingredient-in the form of nutritional supplements-can specifically target visceral fat, a combination of measures can result in an overall loss of calories, excess fat, and visceral fat. Exercise, together with healthier eating, has been shown very effective in reducing overall and visceral fat. According to ingredient suppliers, certain nutritional ingredients have also shown results-by way of mechanisms such as thermogenesis and lipolysis.

Lipolysis is the breakdown of fat, before it can be burned, into smaller particles of free fatty acids and glycerol. Thermogenesis is the production of heat/energy in the body-metabolism-that burns calories and the rate at which fat is released from body stores and broken down to help burn calories.

However, many point out, just as there is more need to identify the mechanisms linking visceral fat to health detriments, there is a need for more research by the supplements industry to explore how ingredients may address visceral fat.

“Visceral-fat management is an area that still needs more focus,” says Nutraceuticals International’s (Elmwood Park, NJ) managing director David Romeo. “A vast array of weight-management supplements and ingredients do not act against visceral fat, and consumers are mistakenly using weight-management ingredients for reducing visceral fat.”

Still, according to companies, several ingredients show promising effects on fat in general. Some may even result in visceral fat loss.

Bitter Orange Extract

One contender in the thermogenic category is Nutratech’s (West Caldwell, NJ) patented Advantra Z (Citrus aurantium). Nutratech’s president Bob Green explains that bitter orange-and specifically its primary protoalkaloidal constituent para-synephrine, or p-synephrine-stimulates the beta-3 receptors on cell walls. These beta-3 receptors are responsible for triggering thermogenesis.

Countering questions that thermogenic ingredients may pose negative cardiovascular effects such as increased blood pressure, Green explains, “Advantra Z works without causing negative cardiovascular and central nervous system side effects. Advantra Z does not cross the fatty membranes of the blood/brain barrier because it is not lipophilic (dissolving in fat or oil). In fact, Advantra Z prefers retention in peripheral tissue rather than passage into the brain. It makes minimal contact with alpha-1, -2, and beta-1, -2 (excitatory) receptors, which are responsible for causing negative cardiovascular and central nervous system side effects.”  

In January, a review in the American Botanical Council’s (Austin, TX) HerbalGram confirmed the safety of bitter orange for human consumption, based on analysis of current research. “No credible adverse events have been directly attributed to bitter orange or its primary protoalkaloid, p-synephrine, in association with oral ingestion,” the authors wrote. (They point out that p-synephrine is often confused with the “m” form of synephrine, which is an FDA-approved over-the-counter drug used in nasal decongestants and sprays and that can constrict blood vessels. M-synephrine does not naturally occur in bitter orange.)

By burning calories and fat, an ingredient like Advantra Z may also result in visceral fat loss-although Green points out that Advantra Z has not been specifically studied for its effects on visceral fat alone. However, he says again, studies have shown overall weight-loss and fat-burning effects.

“Advantra Z does not have a specific mechanism for targeting visceral fat, because there is no such thing as targeted fat burning or targeted weight loss,” says Green. “To lose visceral fat, you have to eat right and exercise. If consumers eat right and exercise, adding dietary supplements than contain thermogenic ingredients like Advantra Z will help speed up the metabolism, giving them the jump-start they need to help shed unwanted visceral fat. After all, thermogenesis is a proven and well-researched method of fat burning and weight loss….Once thermogenesis is triggered-increasing metabolism and the breakdown of fat-many people find that visceral fat is the first kind of fat to go.”
 

Hot Pepper Extracts

Hot pepper is said to increase lipolysis and thermogenic activity. OmniActive Health Technologies’ (Short Hills, NJ) Capsimax ingredient is derived from hot red chili peppers (capsicum).

Capsicum’s active capsaicinoids, which cause the pepper’s hot/spicy flavor, convert to vanillyl amines, which in the brain trigger the release of epinephrine (EP) and norepinephrine (NP) from the adrenal cortex. This release of EP and NP in turn triggers lipolysis. Increased lipolysis enables an increased breakdown of fat, including visceral fat.

“Capsaicinoids have been shown to work on different kinds of target populations-men as well as women, Asian as well as Caucasian subjects, and populations with different levels of fats and carbohydrates in their diets,” says OmniActive’s chief technology officer Jayant Deshpande, PhD. “Research in both animal and human subjects on capsicum and capsaicinoids has indicated significant effects for diet and weight management, including increased energy expenditure, enhanced carbohydrate and fat burning, and reduced caloric intake.”

A study on 10 men and 10 women published last year in Lipids in Health and Disease confirmed Capsimax’s lipolytic effect. The randomized, double-blind, placebo-controlled crossover study compared the results of 100 mg of Capsimax or placebo after 12 hours of overnight fasting. Blood samples were taken 30 minutes before ingestion and then two hours after ingestion. Additionally, blood samples were taken one minute following the end of 30 minutes of exercise (2.5 hours after ingestion) and then again 90 minutes after exercising (4 hours after ingestion).

Compared to the placebo group, the Capsimax group saw significant increases in free fatty acids and glycerol in the blood-indicating that in combination with exercise, Capsimax may increase lipolysis. Moreover, results showed no adverse impact on heart rate or systolic/diastolic blood pressure.

Deshpande says another study showed that Capsimax helps burn more calories. “We believe both these studies together show positive results on key components of success in a balanced weight-management program,”  he says.

To prevent capsicum from irritating the mouth and stomach during oral intake, OmniActive encapsulates Capsimax’s capsaicinoids in OmniBead beadlets. At the right pH level, these beadlets release capsaicinoids in the small intestine.

Another lipolysis-inducing pepper ingredient on the market is Ajinomoto’s (Fort Lee, NJ) Capsiate Natura. The ingredient is derived from a sweet pepper, CH-19, which the company says contains high amounts of beneficial capsinoids (an analog of capsaicinoids) but little capsaicin (the active component that causes spiciness). “To put this in perspective, the Habanero pepper, known as one of the hottest or most pungent peppers, contains very high amounts of capsaicin and very low amounts of capsinoids,” says Yasufumi Furuhata, PhD, Institute of Food Sciences & Technologies at Ajinomoto Company, Inc.

The thermogenic effect of Capsiate Natura-which the company says has shown to result in increased metabolic rates and significant decreases in body weight-involves stimulation of the sympathetic nerve system through activation of a capsaicin receptor, TRPV1, in the gut.

“The activation of the sympathetic nerve system increases the expression of uncoupling proteins-key mediators of fat metabolism found in adipose tissue and skeletal muscle,” says Furuhata. “Some scientists assume that the increase of the uncoupling protein expression will lead to the utilization of fatty acid and help suppress fat accumulation.” The company says that mice treated for two weeks with capsinoids showed increased metabolic rates and significant decreases in body weight.

“Furthermore,” Furuhata adds, “epididymal and peri-renal fat deposits were smaller in the capsinoids group compared to the control group. This means that there was significantly less visceral fat accumulation in mice. The effect observed in animals might occur in humans.”

This explanation may be supported by a 40-subject human study on capsinoids and abdominal fat loss published in 2009 in the American Journal of Clinical Nutrition. This study showed that while there was no significant group difference in the total change in fat, abdominal fat did decrease more in the capsinoid group compared to placebo-which also correlated with a change in body weight. Furthermore, there was a nearly significant increase in fat oxidation in the capsinoid group as well.

“Although it is not pathologically identified in this study how the reduction of excess abdominal fat contributes to the visceral fat loss, the epidemiologic discussion has supported that the abdominal obesity is mainly contributed by the accumulation of visceral fat. A potential explanation for such a tissue-specific fat-mass reduction may be that tissues such as visceral adipose tissue have higher beta-adrenergic receptor density and adrenergic sensitivity-and therefore [exhibit] more visceral lipolysis,” says Furuhata. Studies have shown that it may be long-term ingestion of capsinoids that cause increases in energy metabolism and fat oxidation, he says, adding that further research on capsinoids’ effects on visceral fat are needed.

“We have never positioned capsinoids of Capsiate Natura to be something like a ‘magic pill,’ because it’s not,” adds Jun Tashiro, associate director of Ajinomoto U.S.A. Inc. “Weight management can only be possible in conjunction with diet control and exercise regimen, and capsinoids or Capsiate Natura should be considered to be a piece of the puzzle within the whole weight-management concept.”

7-Oxo DHEA

Also part of the thermogenic equation, 7-Keto is the brand name for a metabolite of the hormone dehydroepiandrosterone (DHEA). It activates three key thermogenic enzymes (glycerol-3-phosphate dehydrogenase, malic enzyme, and fatty acyl CoA oxidase). Developed and owned by Humanetics Corp. (Eden Prairie, MN), 7-Keto is exclusively distributed by Nutra Bridge (Shoreview, MN).

“7-Keto is naturally found in our bodies but declines dramatically with age,” explains Scott Steil, president of Nutra Bridge. “Typically, a person loses about 50% of their endogenous 7-Keto levels by age 40. This results in our bodies’ inability to burn fat like they used to when we were younger.” This is where supplementation can help.

Unlike other DHEA hormone metabolites, 7-Keto (3-acetyl-7-oxo dehydroepiandrosterone, or 7-oxo DHEA) increases thermogenesis by increasing the activity of fat-burning enzymes. In addition, although 7-Keto is a hormone precursor, the 7-Keto metabolite does not affect hormone levels and does not form other active hormone metabolites, such as testosterone or estrogen.

According to Steil, multiple published clinical studies involving more than 150 subjects have shown that 7-Keto increases metabolism by 5.4% compared to placebo (diet). Moreover, it produced 200% greater weight loss compared to placebo (diet and exercise)-which translates to an average additional five pounds lost. Notably, most of this weight loss was in the form of pure body fat (an average of 70 to 80% pure fat).

Steil says that while the companies have not performed specific studies focused only on visceral fat, “The beauty of 7-Keto is that it helps the body convert stored fat to energy, so it works on any part of the body that contains stored fat.” However, with previous 7-Keto studies showing reductions in hip circumference compared to placebo, Humanetics is designing a new clinical study that Steil says will measure changes in visceral fat.

Of note, a 2004 study published in the Journal of the American Medical Association showed that 50 mg of DHEA (not 7-Keto’s specific metabolite) produced significant decreases in both visceral and subcutaneous abdominal fat. Women saw decreases in visceral fat up to 10.2%, while men saw up to 7.4%; for abdominal fat, both sexes saw about 6% decrease. However, Steil says, “This is an interesting study, but is contradicted in multiple clinical studies where DHEA did nothing for weight loss or visceral fat reduction. In general, DHEA has no support for weight-loss claims and is not used in products from serious companies.”

Because the ingredient operates as a nonstimulant, the companies say its thermogenic effects are safe. In fact, says Steil, 7-Keto is the only weight-loss product that has successfully filed two New Dietary Ingredient notifications with FDA.

“7-Keto is the only weight-loss ingredient that is naturally found in the human body,” he adds. “By using 7-Keto, you can help replace what Mother Nature takes away with time and restore the body’s ability to burn fat.”

Fucoxanthin

A carotenoid from brown seaweed, fucoxanthin has also shown nonstimulant thermogenic benefits. Although its mechanisms have not been fully explored, and more human studies are needed, in animal studies fucoxanthin may have caused increased expression of the gene UCP-1, which in turn may help increase fat burning in white adipose tissue as well as fatty acid oxidation.

P.L. Thomas (Morristown, NJ) published a 16-week, 151-subject human study in Diabetes, Obesity, and Metabolism last year on Xanthigen, its ingredient comprising brown seaweed extracts from Laminaria japonica and Undaria pinnatifida, as well as pomegranate seed oil (Punica granatum). The study looked at Xanthigen’s effects on nonalcoholic fatty liver disease (NAFLD). (The company believes that helping to clear excess fatty acids from the liver may result in overall reductions in fat and weight.) The company says the study showed a reduction in body weight-the majority of which was due to a loss of body fat-as well as an increase in resting metabolic rate. Moreover, Xanthigen subjects on average had reduced waistlines.

Nutraceuticals International markets a patented fucoxanthin extract from Japanese wakame seaweed (Undaria pinnatifida) called FucoPure. It says the ingredient is superior because it is highly concentrated. While seaweed itself typically contains only 0.01% fucoxanthin, Nutraceuticals International’s patented extraction process generates an extract that is 10% fucoxanthin, measured by high-performance liquid chromatography. This equates to a 20% fucoxanthin content when measured by UV testing. Comparatively, the company says, most competing material on the market contains only 10% fucoxanthin when measured by UV.
 

Piper betle, Dolichos biflorus Extract

Introduced last year by InterHealth Nutraceuticals (Benicia, CA), LOWAT is a patent-pending blend of two ayurvedic plants, Piper betle leaf extract and Dolichos biflorus extract. The ingredient is said to aid lipolysis, the “gradual and continuous” breakdown of fat.

According to InterHealth, what makes LOWAT unique is that it addresses fat accumulation in the body on two fronts-by decreasing the generation of fat as well as increasing the breakdown of stored fat.

In addition, LOWAT has been shown to increase adiponectin levels. Adiponectin, as mentioned earlier, helps manage glucose levels, and it has also been inversely related to visceral fat mass, says InterHealth.

“In addition to in vitro data demonstrating decreased fat accumulation and increased fat breakdown, clinical research demonstrates that subjects taking LOWAT had a 15% increase in serum adiponectin concentration compared to placebo,” says Paul Dijkstra, InterHealth’s CEO. “This observation suggests a possible reduction in fat stores in supplemented subjects, since adiponectin increases the burning of fat for energy and is inversely correlated to body fat percentage. Increased concentrations of adiponectin are also inversely related to visceral fat mass and visceral fat area.”

These results were presented at the 2010 American College of Nutrition annual meeting last October and at the 2011 Experimental Biology meeting this April.
 

CLA

The fatty acid conjugated linoleic acid (CLA) has effects both on fat storage and fat breakdown.

“Mechanistic studies suggest that CLA has two main sites of action: adipose tissue, the main site of fat storage; and skeletal muscle tissue, the principle site where fat is burned for energy,” explains Christina Ehrhardt, global research manager for Cognis Nutrition & Health (La Grange, IL), now part of BASF. “It has been proposed that CLA decreases body fat mass by inhibiting the amount of fat deposited after a meal and increasing the rate of fat degradation in fat cells, or lipolysis, while at the same time increasing the rate at which muscle cells burn fat (beta-oxidation).”

Cognis’s Tonalin CLA, derived from safflower oil, does not contain thermogenic ingredients. The company says Tonalin’s most significant long-term study (more than 18 human clinical studies have been performed on Tonalin) is a one-year, 180-subject, randomized, double-blind, placebo-controlled study published in 2004 in the American Journal of Clinical Nutrition. It showed that the ingredient reduced body fat by up to 10%, as well as prevented fat regain.

In addition, Tonalin has shown to maintain lean muscle mass by decreasing muscle protein breakdown. More lean muscle mass means increased metabolism-and increased calorie and fat burning.

Tonalin has also shown benefits for abdominal fat mass-which may also translate to benefits for decreasing visceral fat. One study specifically measured the effect of CLA on abdominal fat mass in subjects with metabolic syndrome. The company says that after supplementation with Tonalin, subjects showed significant reductions in sagittal abdominal diameter, representing visceral and total abdominal fat mass. “Sagittal abdominal diameter has been described to be one of the best simple anthropometric measurements of visceral fat and is strongly related to cardiovascular risk,” says Ehrhardt.

Caralluma fimbriata

Gencor Pacific’s (Anaheim, CA) Slimaluma, from the succulent plant Caralluma fimbriata, has been shown to reduce waist adiposity, the company says. Although the ingredient is marketed primarily for its appetite-suppressing effects, the company points to studies it says may also show benefits on visceral fat.

Slimaluma’s effects on abdominal adiposity were shown in a 50-human subject, two-month, randomized, placebo-controlled trial published in Appetite in 2006. In addition to reduced hunger levels, researchers found that although there were no significant decreases in body weight, waist circumference declined significantly in the Slimaluma group.

“It is not clear why the waist circumference specifically declined in this study independent of body weight,” the researchers wrote. “While one possibility is that this was simply an early indicator over the relatively short intervention, the other possibility is that fat in different depots of the body have different rates of lipolysis during negative energy balance or fasting (Monzon, Basile, Henghan, Udupi, & Green, 2002), if it can be assumed that there was a negative energy balance induced by the intake of Caralluma extract. Even under lipolytic stimuli like noradrenaline stimulation for instance, subcutaneous fat in the anterior abdominal wall has a different rates [sic] of lipolysis when compared with whole body lipolytic rates (Kurpad et al., 1994).”

Looking further into the mechanisms of Slimaluma on fat, a mouse cell study, which Gencor’s managing director R.V Venkatesh says was recently accepted for publication in Food and Nutrition Sciences, postulates that Slimaluma inhibits adipocyte differentiation. In other words, it may prevent the multiplication of new fat cells by slowing cell division-thereby preventing weight gain from the subsequent formation of adipose tissue.

“Following weight loss, adipocyte size is reduce by lipolysis, but adipocyte numbers are maintained, facilitating subsequent weight regain,” the authors write. “Since the degree of obesity is linked to adipocyte numbers, inhibiting differentiation and proliferation of pre-adipocytes is an interesting therapeutic strategy.”
 

Future Opportunities

As more health professionals educate patients on the role of fat and visceral fat in overall health, there is also potential for fat and visceral fat to become an increasing topic of focus in the weight-management supplements industry. For industry, educating consumers about the importance of managing fat and visceral fat may be the first step.

“Consumers are well aware of the need to reduce belly fat or a ‘spare tire,’ as it is commonly called. But the concern typically is more about appearance than health,” says Laura Troha, brand management and marketing communications manager for Cognis Nutrition & Health, now part of BASF. “We need to work harder to educate consumers about the health implications of visceral fat.”

“I doubt that many consumers even know what ‘visceral fat’ means, much less how it affects their health,” says Nutratech’s Green. “There’s a lot we can do to promote understanding of visceral fat and its health risks.”

“Today’s consumer is not educated in the dangers of having excess visceral fat,” agrees Nutra Bridge’s Steil. “In fact, as an industry, we are still trying to educate the population about the negative health consequences of being overweight or obese, versus simply improving how one looks or fits into their clothes.”

“There is a beginning awareness about visceral fat and its effects on health,” says Gencor’s Venkatesh. “This area has not yet been widely promoted in the weight-management category of dietary ingredients. It is an area that we are focusing on for Slimaluma, to educate consumers on the risks of visceral fat and the need to reduce it.”    

“To our knowledge, there are not many dietary supplements that target visceral fat or white adipose tissue specifically,” says Ajinomoto’s Furuhata. “As this could be an emerging segment within the weight-management category, there is a real need for safe, scientifically proven compounds that address white adipose tissue.”

Sidebar:

Animal Buzz: Could Hi-Maize Resistant Starch Affect Body Fat?

Resistant starch (starch that resists digestion) has been touted by some as a low-glycemic carbohydrate that helps the body maintain healthy blood sugar levels, improves insulin metabolism, and promotes satiety. According to National Starch Food Innovation (Bridgewater, NJ), resistant starch, and specifically the company’s Hi-maize resistant starch, may also reduce body fat-at least in animal studies-when compared to high-glycemic starch that is easily digested and absorbed as glucose.

Among the mice and rat studies the company cites, one comparing the effects of high-glycemic starch versus Hi-maize resistant starch in mice concluded that while both groups gained weight, the group fed high-glycemic starch gained more weight in adipose fat rather than lean tissue mass, compared to the group fed high-resistant starch. Other studies comparing low- and high-resistant starches found that mice fed high-resistant starch showed significantly lower adiposity, including abdominal adiposity. The high-glycemic diet exhibited a marked, rapid-onset increase in body fat mass and liver fat, whereas the resistant starch diet did not. According to Rhonda Witwer, senior business development manager of nutrition, these effects may be the result of Hi-maize resistant starch improving insulin sensitivity and insulin resistance, because insulin is a principal hormone regulating fat metabolism.