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In December of 2006, Robert Lustig ’77 was sifting through journal articles on liver disease in preparation for a talk on obesity for an environmental-health symposium when he was struck by a realization about sugar. Little did he realize that his simple insight would change the course of his career—and quite possibly change the way all of us eat.

Lustig, an endocrinologist and professor of pediatrics at the University of California, San Francisco, was already an authority on childhood obesity and director of the university’s weight assessment program for kids and teens, but he wasn’t yet the famous antisugar crusader he is today. He hadn’t yet been featured in the New York Times Magazine or appeared on 60 Minutes. He hadn’t published his popular book, Fat Chance, or exchanged barbs with Stephen Colbert on The Colbert Report.

And so when asked to discuss why so many of us were becoming obese and sick, he didn’t yet have a good answer. He understood that the hormone insulin plays a role in obesity. The children with brain tumors whom he’d cared for at St. Jude Children’s Research Hospital in Memphis often suffered from hypothalamic damage, either from the cancer itself or from the treatment, and many of them became obese. Following up on suspicions posited in the 1970s by other researchers, Lustig had shown in 1999 that those obese patients had increased activity of the vagus nerve, which in turn led to greater insulin secretion. When he administered an insulin-­suppressive agent, they lost weight and became more active.

Although Lustig understood that elevated insulin levels were linked to obesity, he hadn’t focused on the relationship between insulin and sugar. Like most other medical professionals at the time, he thought all calories were essentially alike in their ability to make us fat. The problem with sugar, this line of thinking goes, is that it provides only empty calories, negligible in nutritional value.

And yet as Lustig began to look more closely at the literature on sugar in preparation for the symposium, a different picture emerged. Table sugar, or sucrose, is made up of equal parts glucose and fructose, but it was the molecule of fructose that grabbed his attention. Fructose didn’t seem to act at all like most substances we consume. Rather, Lustig realized, it behaved like one particular substance: alcohol.

In some ways, the connection between alcohol and fructose was obvious enough. After all, fermentation can turn both glucose and fructose into alcohol. But while glucose is metabolized by every cell in the body, fructose—like alcohol—is primarily metabolized in the liver, where some of it is converted into fat through a process known as de novo lipogenesis. Consume enough fructose and you could very well end up not only increasing the fat in your blood but also fattening your liver, just as you might by drinking too much alcohol. In fact, that’s exactly what happens in rodents. “I started to research the sugar literature, and it was almost like a one-to-one match,” Lustig says of the similarities between the metabolism of fructose and alcohol. This led him to his controversial conclusion: consumed chronically in large amounts—that is, the way most of us consume it—sugar is poison.

Scientists are still unraveling the biological mechanism at work and sorting out exactly how much fructose might be too much in humans. What’s clear is that fructose and glucose are metabolized very differently, and that unlike glucose, which is the body’s main source of energy, fructose isn’t biologically necessary. Although humans have always consumed carbohydrates, which we convert into glucose, essentially all the fructose we ate before the rise of the worldwide sugar industry 500 years ago came from the small amount in fruits and honey. (The natural fructose in fruit isn’t thought to be a health concern because the fruit’s fiber and cellular structure slow down the rate at which it hits the liver.)

Glucose, too, can be dangerous in excess, Lustig acknowledges. The glucose from our meals that doesn’t end up being used for fuel or stored in the form of glycogen can also end up as liver fat. And whether it’s being driven by fructose or glucose, this accumulation of liver fat appears to be the first step toward insulin resistance and increased insulin levels—the same phenomenon that was making Lustig’s young cancer patients obese. Worse yet, insulin resistance is believed to contribute to a cascade of other metabolic disorders that result in type 2 diabetes, heart disease, and even many cancers. Either way, sugar looked like a villain.

Lustig feared that he would be booed off the stage when he delivered this news to the environmental-health scientists. After all, he was doing much more than telling them that their favorite foods could be toxic. He was also challenging the medical establishment’s most basic dietary advice. For decades Americans had been warned by doctors, scientists, and government agencies that eating too much fat, particularly saturated fat, would clog their arteries and shorten their lives. Now one of the nation’s experts on childhood obesity was declaring that maybe everyone had been focusing on the wrong target. Or, as Lustig would later declare, “It ain’t the fat, people.”

Lustig set out to learn as much as he could on the subject. And the more he learned, the worse the picture looked. Each day, Americans were consuming a startling 22 teaspoons of “added” sugar—that is, sugar beyond the naturally occurring fructose in fruit or lactose in dairy products. Lustig believes that amount far exceeds what our livers can handle. The safe upper limit, both he and the American Heart Association believe, is four teaspoons of added sugar per day for children, six for women, and nine for men (nine teaspoons—or 36 grams—is about what you’ll find in a typical 12-ounce can of soda). More troubling yet, sugar is no longer something manufacturers add only to sweets. Today, it’s almost impossible to avoid. “Of the 600,000 items in the American grocery store, 77 percent of them have added sugar,” Lustig says. “You can’t even reduce your consumption when you’re trying to.”

chart

Source: American Heart Association 2009

Although Lustig quickly made an impression in public-health circles, it wasn’t until July 2009, when University of California Television posted one of his lectures on YouTube, that he reached a mainstream audience. The lecture, called “Sugar: The Bitter Truth,” is an hour and a half long and packed with scientific data on fructose metabolism. In other words, it isn’t exactly the type of video that has “Internet sensation” written all over it. And yet, it has been viewed more than four million times.

Why did a long scientific lecture go viral? It turns out that Lustig, who has authored more than 100 research articles and is the former chairman of the Obesity Task Force of the Pediatric Endocrine Society, is also a veteran performer.

In “Sugar: The Bitter Truth,” his talents for public speaking are on full display. Between the graphs and the dense scientific explanations, he peppers the talk with personal anecdotes about his childhood, long dramatic pauses, provocative statements (he calls fructose “alcohol without the buzz”), and plenty of tantalizing, if unproven, claims—he not only suggests that Coke includes lots of salt to make us thirstier (and extra sugar to cover the taste of all that salt) but dubs this supposed scheme “the Coca-Cola conspiracy.”

“Lustig deservedly gets attention for his ideas, not least because he’s fun,” says Marion Nestle, a New York University nutritionist and the author of the book Food Politics. “He is a master of exaggeration and hyperbole, but underneath all that, he really knows what he’s talking about and cares deeply about keeping kids healthy.”

Lustig, who lives with his wife and two daughters in San Francisco, can trace his foundations in science to his undergraduate days at MIT. He credits 20.30, Sanford A. Miller’s course in nutritional biochemistry, with spurring his curiosity about diet and nutrition. (Miller would later serve as director of the FDA’s Center for Food Safety and Applied Nutrition.) But Lustig’s MIT experience also contributed to his ability to engage an audience. In the three years he spent at the Institute, he managed to be involved in 14 plays, acting in most of them. “It taught me how to get on stage and how not to be scared,” he says.

If Lustig’s gift for public speaking has earned him a lot of online fans, some of his fellow researchers seem less enthused by what they see as his willingness to make bold claims that aren’t substantiated by the scientific literature. Critics point out that the strongest evidence against fructose comes from animal studies, which can’t tell us very much about our own metabolism. Other studies that point to the hazards of sugar, if not fructose specifically, generally are not controlled experiments but merely associations observed between the foods consumed in certain countries (or by specific groups of people) and the health problems those people later develop. Even though such studies may receive a lot of media attention, they can’t conclusively show that sugar is driving the disease process. And while small clinical trials with human subjects have pointed to the dangers of fructose—one 2009 study found that a single week of fructose overfeeding could increase triglycerides (associated with cardiovascular disease) and decrease insulin sensitivity—the large, randomly controlled trials that might provide a more definitive answer would be extremely difficult to carry out.

Luc Tappy, a researcher at the University of Lausanne in Switzerland and a leading authority on fructose metabolism, isn’t yet convinced about the dangers of fructose. In a 2012 paper, he wrote that for humans, “there is no solid evidence that fructose, when consumed in moderate amounts, has deleterious effects.” Though Tappy doesn’t question the honesty of Lustig’s intentions, he says he should not be relied upon as a scientific expert on the topic: “He certainly does not provide a balanced view of things.”

But if Tappy has doubts about Lustig’s presentation of the science, he also thinks he has played a key role in bringing the sugar debate to the public. “At some stage, you have to take decisions without knowing everything, because it would take forever to collect all relevant scientific data,” he says.

Lustig refutes the idea that he’s more provocateur than scientist. He says he wouldn’t be sticking his neck out if he didn’t believe that the science supported his claims. “The science is there,” he insists. He recently coauthored both The Fat Chance Cookbook and a study in the journal PLOS One that shows a strong link between the amount of sugar in a country’s food supply and the prevalence of diabetes in that country. And last year he earned a master of studies in law from the UC Hastings College of the Law in order to better understand how to influence public policy. His ultimate goal is to see fructose removed from the FDA’s list of foods that are “generally recognized as safe.” He points to the recent announcement that the FDA plans to take trans fats off the list—a change that came after 25 years of scientific debate—as evidence that such change is possible.

Lustig may not have to wait a quarter of a century to see some of the steps he seeks. In February the FDA proposed major changes to nutrition labels on food packages. One of those changes: a new line that would highlight added sugars.

“I can’t take credit, and they most certainly won’t bestow it,” Lustig says. “But it does validate the work I’ve been doing.”

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Credit: Photos by Adam DeTour, styling by Catrine Kelty

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