Fat Wars

Chlori-Bar.

A fruit-based micronutrient and fibre-dense supplement bar (the “CHORI-bar”) conceived by Drs. Bruce Ames and Mark K. Shigenaga at Children’s Hospital Oakland Research Institute (CHORI), was shown in clinical trials to improve metabolism in overweight/obese (OW/OB) otherwise healthy adults in ways that are consistent with reduced risk of type 2 diabetes and cardiovascular disease. Consumption of the bar for two months also reduced chronic inflammation, and initiated a reduction in weight and waist circumference. Decreased inflammation and improved weight and weight distribution can lower the risk of many chronic diseases.

These effects occurred without requiring that participants make any change in their current diet or other lifestyle practices other than to eat two CHORI-bars each day for two months. The CHORI-bar is not just another nutrition bar. It is a serious intervention to improve health. Its composition is therefore complex, and required a number of years and a series of clinical trials to develop.

The publication describing this work appeared online at The FASEB Journal. The bar was developed over the past 10 years by a team of scientists led by Drs. Bruce N. Ames and Joyce C. McCann at CHORI, in collaboration with the United States Department of Agriculture (USDA).

Most people do not eat an optimally nutritious diet, particularly the obese. This results in unhealthy metabolism, which not only diminishes vigour, but increases future risk of many diseases. While poor diets contain much that is not healthy (e.g., too much salt, sugar), they also are missing or deficient in a number of important components (e.g., vitamins/minerals, omega-3 fatty acids, fibre) necessary for healthy metabolism. The CHORI-bar is intended to fill these gaps with components present in the bar in normal dietary amounts.

Considerable evidence in the scientific literature, including Drs. Ames and McCann’s work on vitamins and minerals, supports the idea that simply supplying missing or deficient dietary ingredients will improve metabolism. Development of the CHORI-bar has also been guided by Dr. Mark Shigenaga’s insights into the importance of a healthy gut supported by optimal nutrition for disease prevention.

Because of the strong flavours associated with some vitamins and minerals, CHORI partnered with the United States Department of Agriculture to produce a tasty bar. Formulation development was guided by over 15 small clinical trials to ensure that beneficial properties of the bar were retained. Most early trials were two weeks in length and involved primarily lean individuals, most of whom benefited by increased HDL cholesterol. Results presented in this publication are compiled from 3 two-month clinical trials that also included a significant number of overweight/obese individuals. These trials were conducted over a 4-year period using very similar bar formulations. These trials employed a simple, economical design in which participants acted as their own controls (i.e., change in metabolic markers was measured before and after eating the bar).

Healthy metabolism is like a complex, smooth-running machine. Unhealthy metabolism is like an old machine with many rusted out joints. There is no magic bullet ingredient in nutrition, “oiling” one joint is not going to allow the rusted out machine to run. The CHORI-team thinks the broad scale improvements observed with the CHORI-bar may be the result of “oiling” multiple joints by the complex nutrient mixture. They are currently conducting experiments to better understand which ingredients in the bar are most important in the complex mixture for the observed effects.

The increasing prevalence of obesity is taking a huge toll on public health. Conventional approaches that encourage weight loss by improving dietary habits, reducing caloric intake and modifying activity can be successful, but prove difficult for many to initiate and sustain. The CHORI-bar is intended as a non-traditional means to positively impact the obesity epidemic by initiating a healthier metabolism without requiring sudden drastic behavioural changes. It may therefore assist in weight loss programs by beginning a process of favourable metabolic change. Improved metabolism resulting from eating the bar is also associated with a number of reports of feeling better (though this observation has not yet been formally tested), which the CHORI team predicts will help people transition to improved lifestyle habits.

The power of nutrient-rich, properly formulated food-based supplements, such as the CHORI-bar, to move dysregulated metabolism in a healthy direction may help reverse obesity-associated conditions, and thereby reduce the risk of future chronic diseases. The full potential of food-based supplements to do the work of some drugs without their negative side effects is just beginning to be seriously investigated.


Dietary Capsaicin.

A large percentage of the world’s population, fully one third, by the World Health Organization’s estimates, is currently overweight or obese. This staggering statistic has made finding ways to address obesity a top priority for many scientists around the globe, and now a group of researchers at the University of Wyoming has found promise in the potential of capsaicin, the chief ingredient in chili peppers, as a diet-based supplement.

The temptation to eat fatty foods is often so strong that for many, it can override or overpower any dietary restrictions. As a solution to this problem, a group of researchers at the University of Wyoming developed a novel approach to stimulate energy metabolism without the need to restrict calorie intake.

During the Biophysical Society’s 59th Annual Meeting in Baltimore, the researchers from the laboratory of Dr. Baskaran Thyagarajan, University of Wyoming will describe how dietary capsaicin may stimulate thermogenesis and energy burning by activating its receptors, which are expressed in white and brown fat cells. This may help to prevent and manage obesity and other related health complications such as Type 2 diabetes, high blood pressure, and cardiovascular diseases, though this effect has not yet been demonstrated in carefully-controlled clinical trials.

“Obesity is caused by an imbalance between calorie intake and energy dissipation,” explained Vivek Krishnan, a graduate student working in Baskaran Thyagarajan’s laboratory at the University of Wyoming’s School of Pharmacy, a research group known as “Baskilab.”

“In our bodies, white fat cells store energy and brown fat cells serve as thermogenic (heat produced by burning fat) machinery to burn stored fat. Eating calorie-rich food and a lack of physical activity cause an imbalance in metabolism that leads to obesity.”

While pursuing a strategy for obesity management, our group’s laboratory data revealed that “dietary capsaicin, a chief ‘agonist’ (initiator of a response) of transient receptor potential vanilloid 1 (TRPV1) channel protein. suppresses high-fat-diet-induced obesity,” Krishnan said.

Baskilab has found that high-fat-diet obesity and dietary capsaicin, 0.01 percent of capsaicin in the total high fat diet, prevented high-fat-diet-induced weight gain in trials with wild type mice, but not in mice that genetically lacked TRPV1.

Further, dietary capsaicin didn’t modify food or water intake in these mice, “although it did significantly increase the metabolic activity and energy expenditure in wild type mice fed a high-fat diet, “but not for mice that genetically lack TRPV1” Krishnan noted.

So, Baskilab’s overarching hypothesis is that dietary capsaicin induces browning of white adipose tissue and stimulates thermogenesis to counteract obesity. “The main goal of our work is to expand the knowledge of the mechanism by which capsaicin antagonizes obesity, as well as to advance the proof of principle of the anti-obesity potential of dietary capsaicin. Next, we’ll focus on our longer-term goal of developing TRPV1 agonists as new drug molecules to prevent and treat obesity,” said researchers from Baskilab.

Developing a natural dietary supplement as a strategy to combat obesity can be easily advanced to human clinical trials, according to the researchers. “We envision a nanoparticle-based sustained-release formulation of capsaicin, which is currently under development in our laboratory,” added researchers from Baskilab. “In turn, this will advance a novel dietary supplement-based approach to prevent and treat one of the life-threatening diseases, obesity and its associated complications, in humans.”

The group’s strategy to counteract obesity is expected to form a major focus of future healthcare priorities for both the National Institutes of Health and Department of Defense.

Baskilab has already submitted a patent application for the drug delivery aspect of the discovery.


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