The rise of obesity is usually blamed on too much eating and not enough exercising, but Robert Lustig, MD, a UCSF pediatric neuroendocrinologist, asks us to look beyond the obvious. Yes, more Americans are overweight today than 30 years ago. Kids are still getting heavier, compared with prior generations of kids. That leads some UCSF researchers to warn that heart disease and other health problems will grow in future decades. But behaviors that some might refer to as gluttony and sloth are merely consequences of the true cause of the epidemic, Lustig says. Food was just as abundant before obesity’s ascendance. The problem is the increase in sugar consumption. Sugar both drives fat storage and makes the brain think it is hungry, setting up a “vicious cycle,” according to Lustig.
Robert Lustig, MD
More specifically, it is fructose that is harmful, according to Lustig. Fructose is a component of the two most popular sugars. One is table sugar — sucrose. The other is high-fructose corn syrup. High-fructose corn syrup has become ubiquitous in soft drinks and many other processed foods. Lustig presented his case against fructose in a recent UCSF Mini Medical School course on diet and nutrition, part of a series sponsored by the Osher Lifelong Learning Institute. Audience members may have been surprised to hear such unequivocally strong statements from a researcher. Lustig framed the obesity epidemic as a societal issue that pits the food-selling agenda of federal agencies and profit-seeking behavior of major corporations against public health needs. Lustig quit working in the lab a decade ago. Now he spends more time with pediatric patients. He is on the front lines of the world’s weight woes, treating kids who already are obese, a condition that sets the stage for health problems that begin long before these children become adults. Lustig still conducts clinical research. He evaluates dietary lifestyle, as well as pharmacologic interventions that might hold the pounds at bay. He tracks down associations between diet, lifestyle and health outcomes in an effort to identify biological mechanisms that will explain them.
Insulin and Leptin
Lustig’s own groundbreaking studies more than a decade ago stimulated the development of his controversial ideas about metabolism and biological feedback in weight control. One not-yet-popular idea is that, calorie for calorie, sugar causes more insulin resistance in the liver than other edibles. The pancreas then has to release more insulin to satisfy the liver’s needs. High insulin levels, in turn, interfere with the brain’s receipt of signals from a hormone called leptin, secreted by fat cells, Lustig believes. In the 1990s, Lustig worked with children diagnosed with hypothalamic obesity, a disorder that can occur after brain tumor surgery. The children were making more insulin than was necessary for normal energy storage in fat cells. Lustig thought the kids were not receiving signals from leptin, which helps send a message that the appetite has been sated. Lustig concluded that the children’s brains were fooled into thinking that they were starving. Lustig administered a drug called octreotide, known to block insulin release. Insulin levels fell; the children ate less, lost weight, spontaneously became more active and improved their quality of life. Lustig tried the same treatment with obese adults, and found that a subset responded in the same way as the children with hypothalamic obesity. Eating stimulates secretion of insulin and leptin. The conventional view holds that insulin, like leptin, feeds back in the brain to limit food intake, Lustig explains. But Lustig does not think that chronically elevated insulin levels feed back negatively to curb eating. Instead, chronically elevated insulin blocks leptin’s negative feedback signal, Lustig believes. “Most people think insulin does the same thing as leptin,” he says. “I think it does just the opposite.” Lustig believes that fructose generates greater insulin resistance than other foodstuffs, and that fructose calories, therefore, fail to blunt appetite in the same way as other foods.
A Calorie Is Not Just a Calorie
Lustig also is at odds with mainstream scientific viewpoints when it comes to explaining how fructose is shunted through biochemical pathways and converted into fat and other molecules. Unlike conventional calorie counters, Lustig does not believe all food calories have the same impact on fat storage and energy expenditure, regardless of whether they come from fat, protein or carbohydrate. Fructose, a type of carbohydrate, is not metabolized like other foodstuffs, and not even like glucose, the other major carbohydrate, Lustig says. In addition, Lustig claims that fructose is just as bad as alcohol in causing fat storage in the liver — and in causing fatty liver disease. Lustig advances these controversial ideas primarily by citing already published studies, most of them by other researchers. But he also tries to enlist bench scientists in research collaborations in the hopes that additional studies will prove to others that these ideas are correct.
Sugar No Better Than Fat
Each sucrose molecule consists of one molecule of fructose joined to one molecule of glucose. In the gut, these two components are quickly split apart. High-fructose corn syrup is a less expensive mixture of glucose and fructose. There is no point in belaboring the difference, Lustig says. “High-fructose corn syrup and sucrose are exactly the same,” Lustig says. “They’re equally bad. They’re both poison in high doses.” Over the past century, Americans have increased their fructose consumption from 15 grams per day to 75 grams per day or more, Lustig explains. The trend accelerated beginning about three decades ago, when cheap, easy-to-transport high-fructose corn syrup became widely available. Much of processed food labeled “reduced fat” instead has sugar added to make it more palatable, Lustig says. But when it comes to harmful health effects, sugar is worse than fat, he claims. Consumption of either results in elevated levels of artery-clogging fats being made by the liver and deposited in the bloodstream. But fructose causes even further damage to the liver and to structural proteins of the body while fomenting excessive caloric consumption, Lustig says.
Four Simple Guidelines
Lustig prescribes four simple guidelines for parents coping with kids who are too heavy:
- Get rid of every sugared liquid in the house. Kids should drink only water and milk.
- Provide carbohydrates associated with fiber.
- Wait 20 minutes before serving second portions.
- Have kids buy their “screen time” minute-for-minute with physical activity.
Fructose is abundant in fruit. Fruit is fine, Lustig says, but we should think twice before drinking juice or feeding it to our kids. The fiber in whole fruit contributes to a sense of fullness. Lustig says it is rare to see a child eat more than one orange, but it is common for kids to consume much more sugar and calories as orange juice. Eating fiber also results in less carbohydrate being absorbed in the gut, Lustig notes. In addition, he says, fiber consumption allows the brain to receive a satiety signal sooner than it would otherwise, so we stop eating sooner. Exercise burns only a modest amount of calories, Lustig notes. But it does have other benefits. Exercise improves insulin sensitivity in skeletal muscle, lowering insulin levels in the bloodstream. Exercise reduces stress and, therefore, reduces stress-induced eating, according to Lustig. Lastly, exercise increases metabolic rate. The directive to balance active play with computer, video and TV time is the most difficult one to comply with, Lustig says. But failure to limit sugar intake appears to be the most predictive of poor weight control in children, he adds. “You are not what you eat; you are what you do with what you eat,” Lustig concludes. “And what you do with fructose is particularly dangerous.”
Childhood Obesity: Adrift in the “Limbic Triangle”
Michelle L. Mietus-Snyder and Robert H. Lustig
Annual Review of Medicine 59:147-162 (February 2008)
Childhood Obesity: Behavioral Aberration or Biochemical Drive? Reinterpreting the First Law of Thermodynamics
Robert H. Lustig
Nature Clinical Practice Endocrinology & Metabolism 2(8):447-458 (2006)
Adolescent Overweight and Future Adult Coronary Heart Disease
Kirsten Bibbins-Domingo, Pamela Coxson, Mark T. Pletcher, James Lightwood and Lee Goldman
New England Journal of Medicine, 357(23):2371-2379 (Dec. 6, 2007)
Overweight Adolescents Projected to Have More Heart Disease in Young Adulthood
UCSF News Release, Dec. 5, 2007
Prevalence of Overweight and Obesity in the United States, 1999-2004
Cynthia L. Ogden, Margaret D. Carroll, Lester R. Curtin, Margaret A. McDowell, Carolyn J. Tabak and Katherine M. Flegal
JAMA, 295(13):1549-1555 (April 5, 2006)