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Vol. LXVI, No. 9
April 25, 2014
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Amenable to Math Approach
NIDDK Researchers Review Progress in Understanding Obesity

Dr. Kevin Hall

Dr. Kevin Hall

A mathematical approach to understanding obesity and findings on artificial sweetener use and weight gain were the topics at recent Grand Rounds presentations by two NIDDK researchers in Lipsett Amphitheater.

First, NIDDK senior investigator Dr. Kevin Hall outlined his mathematical model, which accurately predicts weight loss and metabolic changes resulting from various obesity interventions. Later, NIDDK senior clinical investigator Dr. Kristina Rother reviewed conflicting data on whether or not use of artificial sweeteners might underlie weight gain.

When Hall, who originally trained in physics, began his career at NIH, he met a Clinical Center dietitian who was designing weight loss programs based on the 3,500 calorie per pound rule. This weight loss rule—extant since the early 1950s—asserts that if a person cuts 500 calories from his or her daily diet, then it would result in a weight loss of one pound per week.

“It seemed odd to me. If I cut 500 calories from my diet, should I really lose 50 pounds in a year, 100 pounds in 2 years?” said Hall. “Something is wrong with this notion, just on its face.”

When dietitians use the 3,500 calorie rule, Hall thinks they wrongly assume two things: first, when someone loses weight, they lose only body fat; and second, that their energy expenditure stays the same. He devised a mathematical model to account for what happens when people of varying weights, diet and exercise habits try to reduce their weight. The model incorporates the results of well-controlled feeding studies that measured how diet changes metabolism, body weight and composition. Called the “body weight simulator,” Hall’s model, published in The Lancet in 2011, has already attracted more than 1 million unique users. He and his colleagues wanted “a realistic dynamical model…of the effects of obesity interventions.”

To validate the model, Hall compared predicted weight change to actual weight change in people undergoing a variety of diet and exercise interventions. In 2012, he measured changes in body fat, total energy expenditure and resting metabolism of 16 contestants on the television show The Biggest Loser.The show chronicles the efforts of obese adults trying to lose weight.

“Mathematical models can help you put together different data sources in a quantitative way and allow you to make inferences about things that were not measured,” said Hall. In an effort to understand the relative contributions of diet and exercise, Hall’s mathematical model was used to analyze the body composition and metabolism data from the TV show contestants. The model suggests that diet changes were responsible for more weight loss, but the exercise helped spare lean mass and generate more fat loss. Furthermore, continuation of a relatively modest diet and exercise program can help sustain weight loss.

Dr. Kristina Rother pointed out that humans have receptors for the taste of sweetness not only on the tongue and oral pharynx, but also in the lungs, liver, pancreas and gut. And flies are even better equipped: they have such receptors on their wings and feet.

Dr. Kristina Rother pointed out that humans have receptors for the taste of sweetness not only on the tongue and oral pharynx, but also in the lungs, liver, pancreas and gut. And flies are even better equipped: they have such receptors on their wings and feet.

Photos: Ernie Branson

Hall has also applied his model to the U.S. population and showed that development of the obesity epidemic over the past 30 years could be explained by the population eating just one-third of the increased calories in the food supply over the same time period. Two-thirds of the increased per capita food supply since the 1970s was wasted. In recent years, food waste from farm to fork amounts to about 1,400 calories per person per day. The increased food waste since the 1970s, he said, could fully feed 60 million people or alleviate the hunger of 600 million people.

“Really shocking quantities of food and oil and fresh water [spent in agriculture] are being wasted,” he said. “These are not small numbers.”

He concluded by explaining his “push hypothesis of the U.S. obesity epidemic”—improvements in agricultural research along with changes in agriculture policy in recent decades have led to increased food production augmented by pervasive and sophisticated marketing, resulting in more cheap and processed food and ending up in fuller bellies and fuller landfills.

Next, Rother reviewed the evidence on weight gain and artificial sweeteners, also known as sugar substitutes. She pointed out a troubling similarity between the U.S. obesity rate (34.9 percent) and adult daily use of artificial sweeteners (32 percent, in 2010). “There’s a very nice parallel curve, but of course association doesn’t stand for causation.”

She focused on five FDA-approved products: saccharin (300 times sweeter than sugar), aspartame and acesulfame-K (both about 200 times sweeter), sucralose (Splenda, 600 times sweeter than sugar) and neotame (10,000 times sweeter).

“Mathematical models can help you put together different data sources in a quantitative way and allow you to make inferences about things that were not measured,” said Hall.

“Mathematical models can help you put together different data sources in a quantitative way and allow you to make inferences about things that were not measured,” said Hall.

Photos: Ernie Branson

Over the last 30 years, the consumption of artificial sweeteners has been on the rise. By 2010, 32 percent of Americans used artificial sweeteners at least once a day, she said. The increase in sweetener consumption has led some researchers to suggest that long-term artificial sweetener use actually might be contributing to the obesity epidemic.

Rother said the most well-known data that links artificial sweetener use to obesity comes from the San Antonio Heart Study. This large natural history study, which was initiated in 1979, concluded that adults who consumed artificial sweeteners in an amount as little as one diet soda per day were, on average, 4 pounds heavier 7 or 8 years later than those who didn’t drink any.

Rother gave two examples of studies in children and adolescents, in which regular soda was replaced with diet soda in order to reduce the amount of calories. In one study, researchers gave obese teenagers diet drinks or supermarket gift cards. The teenagers who received the gift cards could buy anything. After one year, both groups had gained more weight, but the teenagers who drank diet beverages weighed less than the teenagers who received the gift cards. After 2 years, however, both groups of teenagers weighed about the same.

In another study, Dutch researchers recruited 641 children who used to drink sugar-sweetened beverages. They divided them into two groups: half of the children received either one can of a sugar-sweetened beverage and the other half an artificially sweetened beverage. The children who drank sugary beverages gained more weight than those who drank artificially sweetened beverages. The problem with the study was that they didn’t compare the weight gains to children who just drank water. Thus, the only firm conclusion is that drinking regular soda leads to weight gain.

Rother also cited evidence from in vivo and in vitro studies and two small-scale clinical trials that suggest artificial sweetener use may affect metabolism, including gut hormone and insulin secretion.

“We clearly need to sort this out,” said Rother. “So far, there is no convincing evidence that artificial sweeteners prevent obesity.”


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