Life Extension Magazine®

Issue: Jun 2009

Critical Need For a Multi-Modal Approach to Combat Obesity

Middle-age people often ask why they amass so much body fat while eating less than when they were younger and thinner. Scientists have identifi ed biological factors to explain age-related weight gain, yet effective programs to restore youthful body contours remain elusive. The encouraging news is that there are more clinically documented weight-loss compounds than ever before. Here, we introduce a novel multi-modal nutritional approach to removing excess body fat stores, especially in the abdominal region.

By Julius Goepp, MD.

Critical Need For a Multi-Modal Approach to Combat Obesity

If we travel back to the early 1980s, a diagnosis of AIDS resulted in near-certain death within a year or two. The development of single-agent antiviral drugs provided HIV-infected individuals with only a brief reprieve. It was not until the implementation of multi-modal drug “cocktails” that HIV became a manageable disease.

The successful use of “multi-modal” therapy is by no means limited to HIV treatment. Cardiologists often prescribe multiple drugs (including prescription fish oil and niacin) that function via a wide range of mechanisms to restore the health of those stricken with severe heart disease.

The Age-Related Decrease in Cellular Energy Expenditure

Likewise, progressive oncologists long ago realized that successful cancer treatment mandated the implementation of multi-modal approaches to control malignant cell proliferation.

The scientific community now recognizes the role that obesity plays in the induction of age-related diseases and early death.1 The lethal consequences of even a few extra pounds have led to public outcries that Americans have to shed excess fat.

In this article, we introduce a novel multi-modal nutritional strategy to remove excess body fat stores, especially in the abdominal region. Peer-reviewed scientific studies substantiate impressive results using the individual components of this program. This multi-modal approach is an important first step that overweight and obese individuals should initiate to achieve maximal weight loss.

A question middle-age people ask is why they amass so much body fat while eating less than when they were younger and thinner. Scientists have identified a number of biological factors to explain age-related weight gain, yet effective programs to restore youthful body contours remain elusive.

A major impediment to circumventing the causes of weight gain is the simple fact that there are so many causes. The encouraging news is that there are more scientifically documented weight-loss compounds to neutralize these obesity factors than ever before.

When used in controlled clinical studies, these compounds have demonstrated modest to impressive fat-loss effects. These same benefits are not always duplicated in real world settings. What has yet to be done, up until now, is combine scientifically validated compounds into a multi-modal program that circumvents every known factor involved in excess age-related fat storage.

The Age-Related Decrease in Cellular Energy Expenditure

We know that one factor involved in age-related weight gain is a decrease in resting energy expenditure at the cellular level. What this means in simple terms is that we are not burning fat as energy and instead are storing it in our adipocytes (fat cells). Our bloated outer appearance reflects this relentless engorgement of surplus fat into our adipocytes.

The Age-Related Decrease in Cellular Energy Expenditure

Scientists have found that the decrease in energy expenditure with aging may cause 120-190 excess calories to be stored in the body every day.2 This translates to an extra 13-20 pounds of stored body fat each year.

Based on these data, the restoration of a more youthful metabolic rate is one critical factor in inducing weight loss in aging people. Fortunately, a patented green tea delivery system has been documented to significantly enhance weight loss and reduce abdominal waist circumference in humans.

As you will read, however, this remarkable new green tea phytosome delivery system is only one part of a multi-modal solution to do away with surplus body fat.

The Making of a Superior Green Tea Compound

A number of published studies demonstrate weight-loss effects in response to ingesting green tea or specific tea extracts. A problem identified early on is getting enough of green tea’s active constituents absorbed into the bloodstream and delivered to cells throughout the body.

The Making of a Superior Green Tea Compound

The key components responsible for green tea’s weight-loss benefits are the polyphenol compounds that increase metabolic energy expenditure and hence calorie consumption.3-7 Scientists realized that these polyphenols would be more effective if their absorption from the intestinal tract could be increased and thus deliver more of the metabolically active agent to the tissues.8-11

A group of Italian researchers created biological complexes of purified green tea polyphenols combined with phospholipids. This unique green tea phytosome was shown to increase the polyphenols’ ability to be absorbed after oral ingestion and increase peak plasma levels of the critical green tea polyphenol epigallocatechin gallate (EGCG). After oral ingestion of an equal dose of EGCG complexed with phospho-lipids, the peak plasma level was 138% greater than for EGCG alone! Furthermore, the total amount of EGCG measured over time was about three times greater for the phospholipid complex than for the free form alone!8

Dramatic Weight Loss!

When this purified green tea phytosome was tested on human subjects, the weight-loss effects were rapid and substantial. This in-depth multicenter clinical trial involved 100 significantly overweight participants.8 Half the group received the green tea phytosome (two 150 mg tablets daily). Both groups were placed on reduced calorie diets (approximately 1,850 calories/day for men and 1,350 calories/day for women).

After 45 days, the control group lost an average of around four pounds. The group receiving the green tea phytosome supplement dropped an average of 13 pounds—more than triple the amount of the control group.

After 90 days, the results were virtually unprecedented! The control group that followed the restricted calorie diet alone lost 9.9 pounds. The green tea phytosome-supplemented group shed a total of 30.1 pounds—again more than triple the amount of weight loss compared with the control group!8

Impressive Reduction in Abdominal Circumference

Study subjects in the group receiving the green tea phytosome had a 12% decrease in their body mass index (BMI) compared with only 5% decrease in the diet-alone group.8

In the all-important measurement of waist circumference (abdominal girth), there was a 10% reduction in the green tea phytosome group compared with a 5% reduction in the diet-alone group. Male participants did even better in this category, showing a 14% reduction in waist circumference compared with a 7% reduction in the control group.8

What You Need to Know: A Multi-Modal Approach to Combat Obesity
  • Control of obesity requires attack on multiple fronts, including diet, exercise, and responsible, informed supplementation.
  • Rapidly growing evidence suggests multiple opportunities for intervention and different and complementary sites in the cascade of molecular events that lead to obesity.
  • Extracts of an African tree nut, Irvingia gabonensis, help block calorie absorption from the intestine, up-regulate beneficial adiponectin, improve leptin sensitivity, and suppress an enzyme (glycerol-3-phosphate dehydrogenase), that transforms glucose to stored body fat.
  • Beans and seaweed contribute extracts that further block starch breakdown and sugar absorption, while blunting the postprandial spikes in blood sugar and insulin associated with cardiovascular disease risk.
  • Green tea components can block fat breakdown and absorption while up-regulating metabolic rate to cause more rapid consumption of calories and prevent accumulation of excess energy as fat stores.
  • Combining these supplements provides the potential to utilize their complementary mechanisms of action in an additive fashion, maximizing the ability to prevent and reverse excess body fat and its associated disease risks.

Green Tea Does More Than Boost Metabolic Rate

If increasing resting metabolic rates is all it took to remove excess body fat stores, today’s obesity epidemic would largely disappear. We now know that this is only one part of a multi-modal solution.

Green Tea Does More Than Boost Metabolic Rate

Aging diminishes the ability of our cells to utilize even the reduced amounts of fats and sugars we ingest. This phenomenon is clearly demonstrated by the age-induced increase of glucose, triglycerides, cholesterol, and dangerous fat remnants in our blood. Simply stated, as we age, we have a reduced metabolic capacity to make use of the fats and sugars we eat throughout the day. The result is that our bloodstreams become chronically bloated with artery-clogging and obesity-inducing dietary byproducts.

A proven way to reverse the chronic fat-sugar overload in our blood is to impede its absorption from the digestive tract. While there are drugs that effectively do this, green tea extracts have demonstrated promise as inhibitors of fat absorption.12,13 The ability of green tea to inhibit absorption of ingested fat calories may explain some of the observed vascular risk reduction that had been previously ascribed purely to its antioxidant effects.14

How Green Tea Inhibits Fat Absorption and Fat Accumulation in Cells

French researchers released a landmark paper demonstrating that a green tea extract inhibited the breakdown of fat molecules in the digestive tract that enable these fats to be absorbed from the intestine.12

They found that green tea extract could inhibit fat-digesting enzymes in the stomach and small intestine in animal studies, concluding that “green tea extract exhibiting marked inhibition of digestive lipases is likely to reduce fat digestion in humans.”12

Researchers at Rutgers University demonstrated much more recently that these fat-absorption-reducing effects of green tea extracts could inhibit the development of obesity, the metabolic syndrome, and fatty liver disease in mice.15 Korean researchers last year showed that green tea extracts could reduce weight gain in mice by impeding dietary fat absorption and by modulating activity of the gene target PPAR-gamma.16 In another 2008 report, the same team demonstrated that certain green tea extracts prevent fat from accumulating inside fat cells.17

Reduction of Obesity Factor Blood Markers

The new green tea phytosome demonstrated still other benefits that help to explain how it induced so much fat loss in the human study (described on the previous page).

In the diet-alone control group, total cholesterol dropped 10% and triglycerides by 20%. These reductions are expected in response to a reduction in calorie intake.8 In the green tea phytosome-supplemented group, however, total cholesterol dropped 25% and triglycerides by 33%.8

As will be discussed in this issue of Life Extension®, an important element involved in successful weight loss is to purge excess fat (triglycerides) from the bloodstream. Study subjects taking this green tea phytosome significantly reduced their blood levels of triglycerides (and cholesterol). This may help explain the remarkable reduction of 30.1 pounds of body weight experienced by those receiving this novel polyphenol compound most aptly named TeaSlender™ Green Tea Phytosome.

There has been a veritable explosion of research into how green tea extracts affect every aspect of obesity, from inhibition of fat breakdown and absorption in the digestive tract, to reduction in fat storage within cells, to enhancement of metabolic rate with concomitant increased energy consumption.3,16-18 All of these benefits indicate an important role for green tea in helping to prevent the deadly metabolic syndrome, a constellation of disease risk factors that are often initiated by obesity.19,20

How Carbohydrates Induce Weight Gain

The weight-loss effects of blocking dietary fat absorption are not as profound as one might expect. One reason is that in the aging body, carbohydrates absorbed into the bloodstream are readily transformed into triglycerides, which is the primary form that fat is stored in the adipocytes.

What About Digestive Enzyme Supplements?

Popular supplements used by Life Extension® members are digestive enzyme formulas that contain amylase and lipase pancreatic enzymes. As people age, they often produce less of these digestive enzymes, which results in bloating and other gastrointestinal discomforts after eating large meals.

While there are benefits to taking digestive enzyme supplements, an unintended consequence is that these digestive enzymes may enable aging people to ingest larger-sized meals by providing more enzymes to break down excess food in the digestive tract.

If you are seeking to lose weight and support metabolic health by taking the new Enhanced Irvingia formula (that contains amylase, glucosidase, and lipase inhibitors) and/or prescription drugs such as orlistat (a lipase inhibitor) or acarbose (a glucosidase inhibitor), it would not make sense to take digestive enzyme supplements that provide amylase and lipase at the same time.

The aging body develops a resistance to the ability of insulin to transport glucose into the body’s energy-producing cells. This excess glucose promotes chronic secretion of insulin into the bloodstream (hyper-insulinemia), and chronically elevated insulin levels are associated with excess fat storage and degenerative diseases. As excess glucose accumulates in the blood, it is converted by an enzyme (glycerol-3-phosphate dehydrogenase) into triglycerides for storage in the adipocytes (fat cells).

Scientists refer to the chronic bloodstream-overload of sugars and fats as postprandial disorders. The term postprandial is defined as “after meal.” For significant and sustained fat loss to occur, one should reduce postprandial blood levels of both sugar (glucose) and fat (triglycerides).

Green Tea Does More Than Boost Metabolic Rate

Impeding Carbohydrate Absorption

Blocking the breakdown and absorption of carbohydrates are important points of intervention for losing weight. The objective is to target specific enzymes in the intestine, before calorie-rich carbo-hydrates enter the circulation.

Researchers at the innovative Integrative Medicine Program at the UCLA School of Medicine have been actively exploring this area, using extracts from the common white kidney bean (Phaseolus vulgaris).21 The bean extract attains its effect by blocking the alpha-amylase starch-digesting enzymes in the intestine.22 In order to validate this theory, a study was done where 27 obese adults took either a placebo or the Phaseolus vulgaris extract known to “neutralize” the amylase enzyme.21 After eight weeks, those taking the white bean extract lost 3.8 pounds in weight, and 1.5 inches of abdominal fat. Other important benefits were observed in those taking the Phaseolus vulgaris such as a three-fold reduction in triglyceride levels compared with the placebo recipients. Suppressing blood triglyceride levels is often an important component of a long-term weight-loss program.

In another human study of Phaseolus vulgaris,23 researchers discovered that those who consumed the most carbohydrates lost the most weight. Those study subjects consuming the highest levels of dietary starch and supplemented with Phaseolus vulgaris lost 8.7 pounds compared with only 1.7 pounds in the control group. Even more impressive was the 3.3 inches of belly fat lost in the Phaseolus vulgaris group versus only 1.3 inches in the controls. The conclusions showed that weight loss is attainable with diet modification, exercise, and behavioral interventions and it can be enhanced in people with high starch intakes through the addition of Phaseolus vulgaris to impede absorption of carbohydrate calories.

In a remarkable double-blind study on 60 overweight volunteers, half the study participants received 445 mg a day of Phaseolus vulgaris while the other half were given a placebo.24 Both groups were placed on a 2,000-2,200/day-calorie, carbohydrate-rich diet. After only 30 days, those taking Phaseolus vulgaris lost 6.5 pounds of weight and 1.2 inches in waist size compared with 0.8 pounds and 0.2 inches in the placebo group.

These kinds of studies show the futility of trying to lose weight by restricting caloric intake alone, yet demonstrate remarkable effects when just one natural weight loss compound is combined with reductions in food intake.

Impeding the Alpha-Glucosidase Enzyme

While inhibiting intestinal amylase enzyme activity has demonstrated some fat-loss results, it may be equally important to impede another enzyme needed for carbohydrate absorption called alpha-glucosidase.

European researchers working with extracts of several seaweed species found that extracts of the Fucus vesiculosus (bladder wrack) caused significant reductions in blood glucose eight hours after being given to rabbits.25 Subsequent research has uncovered a host of health benefits from seaweed extracts, including powerful antioxidant, anti-tumor, and vascular health-promoting effects.26-29

Intrigued by these findings, researchers began exploring the antidiabetic properties of various seaweeds, including bladder wrack and Ascophyllum nodosum, also known as brown algae. What they discovered was that these seaweeds were capable of strongly inhibiting the carbohydrate-digesting alpha-glucosidase enzyme in rat intestines.28 Given to diabetic rats in the laboratory, the extracts reduced fasting glucose levels significantly at 14 days and blunted the sharp rise in blood glucose (postprandial effect) following an oral glucose tolerance test. Interestingly, the animals also experienced decreases in total cholesterol and sugar-damaged (glycated) protein levels.

Blood Glucose (mmol/L) Insulin (pmol/L)

Figure 1. Inhibition of glucose absorption by InSea2™ treatment compared with placebo 30 minutes after a meal. InSea2™ reduces postprandial blood glucose levels by 90% compared with placebo (p<0.05).33

Figure 2. Inhibition of insulin secretion by 7.5 mg/kg InSea2™ compared with placebo and the alpha-glucosidase-inhibiting drug acarbose .33 InSea2™ reduces the rise in insulin secretion normally seen 30 minutes after a meal by 40% (p=0.12).

A proprietary combination of extracts from bladder wrack and brown seaweed known as InSea2™, has been shown to help modulate dangerous postprandial sugar swings that lead to increased protein (glycation) damage, abdominal obesity, and food cravings that often come after a meal rich in carbohydrates.30-32 While these results have not yet been published, they reveal important aspects of how these extracts may work to improve metabolic health, a critical component of achieving normal weight.

The formulator of InSea2™ first conducted a series of studies to demonstrate the effect of the extracts on inhibiting the digestive enzymes, amylase and glucosidase. Both enzymes were powerfully inhibited within a few minutes of being exposed to the seaweed extracts. Additionally, they found that when InSea2™ was fed to laboratory animals, glucose levels were reduced by up to 90% following a meal compared with non-supplemented animals. Insulin levels (a measure of insulin sensitivity) were as much as 40% lower in the InSea2™-supplemented rats.33 Clearly, this supplement may provide important benefits in reducing metabolic parameters that impact both systemic health issues as well as weight gain.

Impeding the Alpha-Glucosidase Enzyme

Upon further review of the study data, scientists found another interesting effect in the group supplemented with InSea2™. The normal response to an after-meal spike in blood glucose is a surge in insulin secretion. This insulin surge often causes blood glucose to be driven down too low. This can then create artificial hunger for more calories to elevate the depressed glucose blood levels. In lab animals taking InSea2™, the dramatic post-meal drop in glucose levels did not occur, and their glucose levels returned to baseline levels in a more gradual and natural fashion.

The after-meal drop in blood sugar produces a feeling of fatigue and can foster a sense of increased hunger leading to additional caloric intake. By “smoothing out” the postprandial sugar drop, InSea2™ exerts both biochemical and behavioral benefits on overall calorie intake. In the researchers’ words, “InSea2™ was able to change the absorption profile of a high-glycemic index (GI) food towards that of a low-GI food.”33

The Multiple Biological Effects of Irvingia Gabonensis

Irvingia gabonensis has been used in food preparation for millennia in Africa, where it is prized for its nutritional potential.34,35 Based on its known therapeutic properties, scientists began to examine Irvingia extracts for their ability to achieve glucose control.36 The researchers found that Irvingia supplements produced a reduction in plasma lipid levels, especially the dangerous very low-density lipoprotein (VLDL), LDL, and triglycerides.37 The team went on to study Irvingia’s effect in rats, seeking to understand the molecular reasons for these impressive results.38 What they found was that Irvingia produced a marked reduction in levels of a host of amylase enzymes, culminating in reduced absorption of glucose and concomitantly lower levels in blood and urine.

While Irvingia research continued to focus on its antioxidant and antimicrobial effects,39-42 scientists began exploring its potential for combating obesity. The results of these investigations on weight loss and lipid control were eventually published.43 In the first study, 28 people received the Irvingia supplement and 12 were given a placebo. All subjects stayed with their regular diets. After the month-long study period, the Irvingia group had lost 5.26% of their body weight, whereas placebo recipients shed only 1.32%. As in the older studies, supplemented patients, but not placebo patients, experienced decreases in total cholesterol, LDL, and triglycerides and an increase in HDL.

Stimulated by these findings of Irvingia in human trials, researchers set out to discover exactly how these effects were being obtained. They did this armed with new knowledge about the complex interactions of fat tissue in the metabolic processes, including its influence by, and on, various biochemicals involved in inflammation.44 The researchers focused on three key elements: 1) a substance called PPAR gamma, produced by a gene known to contribute to human obesity; 2) the hormone leptin (which suppresses appetite and increases triglyceride breakdown in adipocytes); and 3) adiponectin (which reduces fat deposition).

Using fat cells from mice, the researchers examined the effects of Irvingia extract on these three important players in the obesity-generating process. After just eight days of treatment, the cells were found to have significantly reduced their production of fat stores. This result occurred in response to the inhibition of an enzyme (glycerol-3-phosphate dehydrogenase) responsible for converting glucose to stored triglyceride in adipocytes. This was accompanied by a decrease in expression of PPAR gamma, with a corresponding increase in the production of the insulin-sensitizing compound adiponectin. These were compelling results —as the researchers concluded that, “[Irvingia] may play an important multifaceted role in the control of adipogenesis [fat production] and have further implications in in-vivo anti-obesity effects.”44

Encouraged by these findings, the researchers progressed to larger human studies. In a recently published study in the journal Lipids in Health and Disease,45 human subjects who supplemented with Irvingia enjoyed significant improvements in body weight, body fat, and waist circumference, while their plasma lipid, adiponectin, and leptin levels were all improved. Interestingly, supplemented subjects also experienced decreases in levels of the inflammatory marker C-reactive protein, which is a known cardiovascular risk factor.46 Reduction of inflammation is now gaining the attention of scientists around the world as another important component for controlling weight and metabolic disorders. The authors’ conclusion is “Irvingia gabonensis extract may prove to be a useful tool in dealing with the emerging global epidemics of obesity, hyperlipidemia, insulin resistance, and their co-morbid conditions.”45

Perhaps one of the most consistent benefits of Irvingia supplementation was a reduction in appetite among study subjects. Avoiding over-consumption of calories remains a critical aspect of a science-based weight-loss program.

Summary

Scientists now recognize many biochemical pathways and control mechanisms that help regulate how we absorb, distribute, and expend ingested food throughout the body. With each new discovery we identify additional points for intervention that can tip the scales in favor of successful reductions in body fat.

Natural supplements whose mechanisms of action are clearly understood are available to help in controlling body weight. Used responsibly and in combination, these nutrients may complement one another and have the potential to yield maximum control over abdomfdrhginal fat, obesity, and cardiovascular health.

Advances in our understanding of the causes of obesity are paying off on multiple fronts. While the nutrients described in this article provide many components of a multi-modal weight-loss program, we encourage members to carefully review all the articles in this month’s issue to fully take advantage of today’s wealth of knowledge about shedding excess fat pounds.

Seven Reasons Why You Don’t Lose Weight, Even When Eating Less!

Tens of millions of Americans struggle to rid themselves of excess body fat—especially in the abdomen. Most do not succeed. Overlooked are the multiple underlying causes of age-related weight gain.

The diagram below highlights many of the biological mechanisms involved in age-related fat accumulation. Once you understand how these obesity factors preclude significant shedding of fat pounds, you are in a position to implement scientific strategies to circumvent them.

FAT ACCUMULATORS

#1 Disrupted command signals

Leptin resistance
Leptin is a hormone that promotes the breakdown of fat in adipocytes and tells the brain to turn off chronic hunger messages. As we age, our cells (including the appetite control center in our brains) become leptin-resistant, meaning that leptin is unable to effectively regulate body weight.

Weight Gain

Low adiponectin levels
Adult-onset weight gain is characterized by enlargement of fat cells. Large fat cells secrete less adiponectin—a crucial hormone that helps support insulin sensitivity.

#2 Chronic bloodstream-overload of fats and sugars

Rapid carbohydrate absorption
Breakdown of large carbohydrate molecules such as starches by enzymes called alpha-amylases in the digestive tract can lead to absorption of calorie-rich carbohydrates into the circulation. Aging diminishes our cells’ ability to utilize even reduced amounts of ingested starch, which is rapidly transformed into triglycerides for fat storage in adipocytes.

Weight Gain

After-meal glucose elevation
Rapid absorption of dietary sugars into the bloodstream by enzymes called alpha-glucosidases can lead to postprandial swings in glucose and insulin that are associated with increased appetite.

#3 Fat storage

Low cellular energy expenditure
A dramatic age-related slow-down in metabolic rate and a decrease in cellular energy expenditure in response to reduced food intake both cause excess calories to be stored as fat within the body.

Conversion of blood
glucose to triglycerides
Excess glucose in the blood is converted into triglycerides for storage in adipocytes by an enzyme called glycerol-3-phosphate dehydrogenase.

Fat absorption
Breakdown and absorption of dietary fats by enzymes called lipases enable the body’s cells to take up and store fat. Fat absorption powerfully increases total caloric uptake since fat contains nine calories per gram, while carbohydrates provide
only four.

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