Adam Voorhes

In January of this year, the first subject checked into the metabolic ward at the National Institutes of Health in Bethesda, Maryland, to participate in one of the most rigorous dietary studies ever devised. For eight weeks, he was forbidden to leave. He spent two days of each week inside tiny airtight rooms known as metabolic chambers, where scientists determined precisely how many calories he was burning by measuring changes in oxygen and carbon dioxide in the air. He received meals through vacuum-sealed portholes so that the researchers' breath wouldn't interfere with their measurements. The food itself had been chemically analyzed to ensure an exact number of carbohydrate, protein, and fat calories.

The two-day stays in the chambers were only a small part of the testing, which was also being carried out on subjects at three other institutions around the US. Twice a month, the subjects were required to lie down for dual-energy x-ray absorpti­ometry scans, an accurate way to measure body fat. They offered up their veins again and again so that scientists could measure their lipids and hormone levels. They provided samples of their stools so the researchers could record the different colonies of bacteria residing in their guts.

And yet for all the poking, prodding, measuring, and testing, the most remarkable thing about the $5 million undertaking may be that it's designed to answer a question you'd think we'd have answered long ago: Do we get fat because we overeat or because of the types of food we eat? The Energy Balance Consortium Study, as it's called, is one of the first to be backed by the Nutrition Science Initiative, a nonprofit that prides itself on funding fanatically careful tests of previously overlooked hypotheses. NuSI (pronounced new-see) was launched in September 2012 by crusading science journalist Gary Taubes and former physician and medical researcher Peter Attia. The three NuSI studies now under way, which focus on establishing the root causes of obesity and its related diseases, provide just a glimpse of Taubes and Attia's sweeping ambition. NuSI has already raised more than $40 million in pledges and is in the midst of a $190 million, three-year campaign to fund a new round of studies that will build off the findings in the initial research. Together, the studies are intended as steps toward an audacious goal: cutting the prevalence of obesity in the US by more than half—and the prevalence of diabetes by 75 percent—in less than 15 years.

THE INITIATIVE HAS AN AMBITIOUS GOAL: CUT THE PREVALENCE OF OBESITY IN THE U.S. BY MORE THAN HALF IN LESS THAN 15 YEARS.

NuSI's strategy is to bring the nation's top nutrition researchers together to find answers as a team. But arriving at a consensus about our nutrition woes won't be easy. Almost as striking as the grim health numbers themselves—two-thirds of American adults are now overweight or obese; more than 115 million Americans have diabetes or prediabetes—is that for all the thousands of studies and billions of dollars we've spent on research, there is no agreement among the experts on why we've grown so much more fat and sick over the past several decades or what we should do about it.

The standard explanation is that Americans eat too much—and especially too much fat, which for a long time was thought to be the underlying cause of obesity and most other chronic diseases. That's why major health organizations such as the American Heart Association and the American Cancer Society continue to recommend diets low in saturated fat, with prominent vegan doctors arguing that the answer to our problems lies in avoiding all animal products.

https://www.youtube.com/embed/dBnniua6-oM The idea that some calories—specifically those from refined carbs—are worse than others was popularized by Robert Lustig in this 2009 video.

The 2014 documentary Fed Up, coproduced by Katie Couric and Laurie David, likens the “sugar industry” to the tobacco industry of 30 years ago.

But in recent years, competing theories have suggested other culprits. A growing number of doctors and advocates now see decades of increased consumption of table sugar and other refined carbohydrates as the most likely explanation for our current epidemics. Robert Lustig, a pediatric endocrinologist, rose to national fame after a 2009 lecture in which he called sugar “poison” went viral on YouTube. (Lustig had a chance to repeat his case against sugar in the 2014 Katie Couric-produced documentary Fed Up.) Meanwhile, newer science has undermined the consensus that fat is all that bad for you. A recent meta-analysis published in the Annals of Internal Medicine found no clear evidence that eating saturated fat contributes to cardiovascular disease. This major study resonated across the cultural landscape, garnering a Time magazine cover (“Eat Butter”) and a public reconsideration of the danger of fat by television host Dr. Mehmet Oz, who had previously preached against high-fat diets.

Taubes and Attia are firmly in the sugar-bad, saturated-fat-good camp. Indeed, Taubes has written a number of the articles and books—including the best-selling Good Calories, Bad Calories—on which that thinking is based. But even they acknowledge they can't be certain. That's because, as Taubes eloquently argues, most of the existing knowledge gathered in the past five decades of research comes from studies marred by inadequate controls, faulty cause-and-effect reasoning, and animal studies that are not applicable to humans. The whole body of literature, Taubes wrote in a blog post announcing the launch of NuSI, “is based on science that was simply not adequate to the task of establishing reliable knowledge.”

For instance, much of what we think we know about nutrition is based on observational studies, a mainstay of major research initiatives like the Nurses' Health Study, which followed more than 120,000 women across the US for three decades. Such studies look for associations between the foods that subjects claim to eat and the diseases they later develop. The problem, as Taubes sees it, is that observational studies may show a link between a food or nutrient and a disease but tell us nothing about whether the food or nutrient is actually causing the disease. It's a classic blunder of confusing correlation with causation—and failing to test conclusions with controlled experiments. “Good scientists will approach new results like they're buying a used car,” he says. “When the salesman tells you it's a great car, you don't take his word for it. You get it checked out.”

NuSI's starting assumption, in other words, is that bad science got us into the state of confusion and ignorance we're in. Now Taubes and Attia want to see if good science can get us out.

Gary Taubes Peter Yang

Perhaps it's no surprise that Taubes, 58, founded a project as daring and ambitious as NuSI. He has a well-deserved reputation for being tough-minded and combative. (His detractors in nutrition science have long accused him of hubris.) He majored in applied physics at Harvard, where he also played on the football team's defensive line. (John Tuke, one of his teammates, recalls that Taubes stood out for his intensity.) After Harvard, Taubes headed to Stanford for a master's in engineering with visions of becoming an astronaut. It was only after realizing that NASA wasn't likely to send a man of his size to space—Taubes is 6′2″ and 220 pounds—that he decided to pursue an interest in investigative reporting that had been sparked by reading All the President's Men.

BUTTER IS BACK

Taubes' 2002 article in The New York Times Magazine led to a book on diet and nutrition.

2002

2007

2014

He attended Columbia University's Graduate School of Journalism and soon landed a job at Discover magazine. He caught a break in 1984, when a profile of particle physicist Carlo Rubbia led to a deal for his first book, Nobel Dreams. Taubes thought he would be documenting a breakthrough in physics. Instead, the book chronicled Rubbia's errors and the machinations he used to outmaneuver his fellow physicists. Taubes was struck that science could be so subjective at the highest levels—that it's not just the big mistakes that scientists have to worry about but the numerous small ones that accumulate to support their misconceptions. “You can be fooled in a thousand subtle ways,” he says.

That lesson stuck with him when, almost by accident, he turned his attention to nutrition science in 1997. By then a freelancer and running low on rent money, he called his editor at Science and asked if there were any assignments he could turn around quickly. The editor mentioned a paper in The New England Journal of Medicine that detailed a dietary approach to reducing blood pressure without restricting salt. Maybe he could write about that?

Taubes knew almost nothing about the topic. He would end up spending the next nine months interviewing 80 researchers, clinicians, and administrators. That research resulted in an August 1998 article headlined “The (Political) Science of Salt.” It was a sweeping takedown of everything scientists thought they had established about the link between salt consumption and blood pressure. The belief that too much salt was the cause of hypertension wasn't based on careful experiments, Taubes wrote, but primarily on observations of the diets of populations with less hypertension. The scientists and health professionals railing against salt didn't seem to notice or care that the diets of those populations might differ in a dozen ways from the diets of populations with more hypertension.

Taubes began to wonder if his critique applied beyond salt, to the rest of nutrition science. After all, one of the researchers Taubes interviewed had taken credit not only for getting Americans to eat less salt but also for getting them to eat less fat and eggs. He kicked off a multiyear research project that culminated in 2002, when he published a New York Times Magazine cover story on fat that would vault him into prominence and onto the path to NuSI.

Under the cover line “What if Fat Doesn't Make You Fat?” Taubes made the case that we get fat not because we ignore the advice of the medical establishment but because we follow it. He argued that carbohydrates, not fat, were more likely to be the cause of the obesity epidemic. The piece was a sensation. “Gary Taubes is ruining my life!” one NYU professor of nutrition, Marion Nestle, complained to Popular Science at the time. “I can't go anywhere without someone asking about that damn article.”

“I lost friends over that story,” Taubes says. “One journalist friend who had written a book about obesity accused me of having a brain transplant.”

The Times article led to a $700,000 deal for what would become Good Calories, Bad Calories, and Taubes spent the next five years plowing through late-19th- and 20th-century nutrition research. In doing so, he found himself drawn to an even more radical theory, the so-called alternative hypothesis, which holds that we get fat not because we eat too many calories but because specific kinds of calories trigger hormones that regulate how our fat cells behave. In particular, eating refined carbohydrates, and especially sugar, on a sustained basis leads to chronically elevated insulin levels. Among its many other crucial functions in the body, insulin tells fat cells to take up glucose, which is converted into fat, and then keeps fat from all sources locked inside. Therefore: Consume a bunch of sugar every day, as most Americans do, and you'll get fat.

Of course, Taubes could only present the hypothesis. He couldn't prove any of it. The right experiments had never been done.

EVEN SKEPTICAL SCIENTISTS ARE EAGER TO WORK ON THE NEW STUDIES. ONE REASON: GENEROUS FUNDING.

By the time Peter Attia read Good Calories, Bad Calories, he already sensed that something was off about nutrition science. He didn't have to look much farther than his own waistline. Attia had taken up endurance swimming in his thirties. (In 2008, at age 34, he became the first person to swim from Maui to Lanai and back.) And yet despite exercising for three to four hours a day and watching what he ate, he'd become fat.

At age 35, Attia weighed 205 pounds, 45 more than he did in high school. Alarmingly, his blood work suggested he was on the path to heart disease. Fearing for his future and out of conventional options, in late 2009 Attia began eliminating more and more carbs from his diet while adding more and more dietary fat. Over the next two years, his waist shrank from 36 to 31 inches. His triglycerides, an indicator of cardiovascular risk, dropped from 154 to 22. His HDL (the so-called good cholesterol) rose from 31 to 85 even as his LDL (the arguably bad cholesterol) dropped from 113 to 59.

In April 2011, Attia sent an email to Taubes, asking a few questions about fructose versus glucose. They eventually agreed to meet at an Oakland, California, café. Attia came prepared with 20 pages of highly technical medical questions. The two men discussed their passionate interest in nutrition science and soon discovered a shared admiration of physicist Richard Feynman. Before long, they decided to start a new organization together. The Feynman Foundation, as it could be called, would recruit world-class scientists from different fields to review existing nutrition literature and create consensus statements.

But the more they discussed the idea, the more unlikely it seemed that mere reviews of the existing literature would be enough to change the consensus about diet. “We decided the only way to do this was to create this Manhattan Project-like entity where you bring in all these scientists and remove that one obstacle”—funding—“that is preventing them from doing what they really need to do,” Attia says. “We wanted to just say, ‘Go out and solve it.’”

“I'd been waiting for someone like Peter to come along for a long time,” Taubes says.

In Attia, Taubes found a partner even more driven than he is. Attia, now a lean endurance cyclist, appears every bit as fit as Taubes. (Both men took up boxing in their youth.) Like Taubes, Attia had planned to study engineering before deciding to go into medicine.

Taubes and Attia's initial plan was to start slowly, raising money on nights and weekends. Then one day in November 2011 a former natural-gas trader named John Arnold sent Taubes a five-line email. He had heard Taubes on a podcast talking about the type of study that could help uncover the triggers of the obesity epidemic. Arnold was listening closely. “From the little I know about the science of nutrition,” he wrote, “your study makes a lot of sense.”

Peter Attia Peter Yang

Taubes had never heard of Arnold. Some quick Googling revealed that he was something of a legend in his field. In 2007, at 33, he became the youngest billionaire in the country. He got his start at Enron before founding his own hedge fund, Centaurus Energy Master Fund, where he proved to be almost preternaturally prescient in making bets on gas prices. In May 2012 Arnold announced that he was closing his fund to focus on philanthropy. Later that month, the Laura and John Arnold Foundation gave NuSI a $4.7 million seed grant. An additional $35.5 million grant was announced last year. “The reason the research hasn't been done right, according to the scientists we've talked to,” says Denis Calabrese, president of the foundation, “is that it's too expensive. And John and Laura said, ‘Well, fine. Tell us how much it is, and let's do it right.’”

So Taubes and Attia have the money and the mission, but what they emphatically don't have—they insist—are prebaked answers to the tough questions they are asking. They are leaving those up to some of the top names in nutrition research—many of whom, as it turns out, are highly dubious of the alternative hypothesis. Consider Kevin Hall, a senior investigator at the NIH's National Institute of Diabetes and Digestive and Kidney Diseases. Like other researchers in the Energy Balance Consortium, he agreed to work with NuSI only once he understood that the initiative would have no control over the study's design, conduct, or reporting.

A physicist by training, Hall has developed a mathematical model that can predict how different diets impact metabolism and body composition. According to Hall's model, the low-carb, low-insulin diet that the participants will eat in the second phase of the metabolic ward study should have at most a tiny effect on the total calories they burn. “I'm currently skeptical,” Hall says of the alternative hypothesis.

Rudolph Leibel, one of the researchers working on the consortium study at Columbia, also has similar doubts—not least because his own research fully supports the calories-in/calories-out model, which holds that all calories have equal impact on our weight. When Leibel had participants in one study drink formulas with the same number of calories but hugely different proportions of fat and carbohydrates, he saw no difference in the amount of energy they burned.

Like Hall, Leibel makes no secret of his doubts about the alternative hypothesis. And considering the lack of love between Taubes and many in the nutrition research community, the most surprising aspect of NuSI may be that these skeptical scientists have agreed to work with the organization in the first place.

One likely explanation is money, or more specifically the science that money makes possible. NuSI is giving researchers an opportunity to carry out unusually ambitious work. The NIH might fund similar studies to the tune of a few hundred thousand dollars a year. “The NIH has a very limited amount of money at a time when science requires increasingly expensive research to answer much more sophisticated questions,” says David Ludwig, a professor of nutrition at the Harvard School of Public Health and director of the New Balance Foundation Obesity Prevention Center at Boston Children's Hospital.

With coprincipal investigator Cara Ebbeling, Ludwig is overseeing a NuSI experiment that launched in July 2013. The $13.6 million study ($10.3 million of which comes from a NuSI grant) also tests the alternative hypothesis on 150 overweight and obese college students, faculty, and staff who are fed most of their meals under direct observation in the school's cafeteria.

In contrast with Hall and Leibel, Ludwig's previous work has supported the alternative hypothesis. And Ludwig is optimistic that NuSI-sponsored science may one day change the way many of us think about nutrition: “One key study could be the hammer that dislodges the loose brick in the prevailing paradigm.”

In March 2013, Christopher Gardner, a professor of medicine and a director at the Stanford Prevention Research Center, began preparing for NuSI's first free-living study—where subjects aren't directly observed as they eat. One of the largest such human experiments ever to test a low-fat diet against a low-carbohydrate diet, Gardner's study stems from his previous research, which suggests a diet's effectiveness may be due to how insulin-resistant the dieter is at the outset. It will randomize 600 overweight-to-obese subjects into two groups. Both will receive regular counseling meant to help them stick to their diets, a standard practice in other free-living studies. But to overcome the major problem with such work—inaccurate accounts of consumption based on volunteers' food diaries—NuSI is funding the creation of an app that allows subjects to record their eating activity by selecting photos from an extensive database. (Because of confidentiality agreements with the developers, Attia wouldn't provide much detail on the app's features.)

The app is just one example of NuSI's ambition to rewrite the rules of nutrition research funding, take huge risks, and arrive at answers as quickly and unambiguously as possible. It's “go big or go home,” says Attia, who runs NuSI's day-to-day operations.

Taubes, too, is aware of the risk. As Calabrese puts it, “Gary is advancing a study that may refute a theory he's built his career on. It may blow his theory right out of the water.”

If that happens, or if NuSI fails to bring any clarity to our obesity epidemic, Taubes won't be totally unprepared. In the entryway of his home, just off the main foyer, there's a frame with two photos in it. In one, taken just before the start of an amateur boxing match, a young Taubes is standing, gloves at his side. In his tank top and boxing shorts, the muscular young man looks powerful enough to punch his way through anything. In the other photo, taken about two minutes later, Taubes is lying on his back unconscious. “It's my hubris protection,” Taubes says. “Whenever I think I'm so cool I can do anything, it reminds me that I am not and that this is real life.”

FINALLY: HARD SCIENCE ABOUT DIET

NuSI was founded on the premise that existing obesity research is rife with error, bad methodology, and flawed assumptions. So NuSI-sponsored scientists are conducting their own elaborate studies in an effort to definitively establish what's making us so fat and how diet affects health. Here's a look at three studies in the works. —VICTORIA TANG

Boston Children's Hospital Study

Purpose: Assessing weight-loss maintenance

Time frame: July 2013 to June 2017

Participants: 150 overweight and obese college students, faculty, and staff

Question: Does the macro­nutrient content of diet—proportion of carbs, fat, and protein—affect fat storage?

Procedure: Subjects live in dormitories for observation. They first lose about 12 percent of their weight on a diet that restricts all calories equally. Then they are randomly assigned one of three diets, with varying proportions of carbs and fat. Scientists closely monitor the subjects for physiological change.

Cost: $13.6 million

Energy Balance Consortium Study

Purpose: Monitoring energy expenditure and appetite

Time frame: September 2013 to December 2014

Participants: 17 overweight and obese males, ages 18 to 50

Question: Does altering carbs and fat in the diet affect calories burned or cause hormonal changes?

Procedure: After four weeks of a standard diet designed to maintain weight, subjects make a drastic switch to a ketogenic diet (5 percent carbs, 80 percent fat) with the same number of calories. If Taubes' hypothesis holds, the change in diet should reduce fat mass and be accompanied by increased energy output.

Cost: $5 million

Stanford University Study

Purpose: Testing diets in the real world

Time frame: March 2013 to December 2016

Participants: 600 overweight and obese subjects, ages 18 to 50

Question: What effect do low-carb and low-fat diets, along with genetic and clinical differences, have on weight loss?

Procedure: In a large so-called free-living study, participants are put on either an extremely low-fat or low-carb diet but are allowed to eat as much protein (and carbs or fat, respectively) as desired. To track daily routines over 12 months, NuSI is developing a smartphone app to monitor eating habits and compliance.

Cost: $7.4 million

FINALLY: HARD SCIENCE ABOUT DIET

—VICTORIA TANG

NuSI was founded on the principle that existing obesity research is rife with error, bad methodology, and flawed assumptions. So NuSI-sponsored scientists are conducting their own elaborate studies in an effort to definitively establish what's making us so fat and how diet affects health. Here's a look at three studies in the works.

Boston Children's Hospital Study

Purpose: Assessing weight-loss maintenance

Time frame: July 2013 to June 2017

Participants: 150 overweight and obese college students, faculty, and staff

Question: Does the macronutrient content of diet—proportion of carbs, fat, and protein—affect fat storage?

Procedure: Subjects live in dormitories for observation. They first lose about 12 percent of their weight on a diet that restricts all calories equally. Then they are randomly assigned one of three diets, with varying proportions of carbs and fat. Scientists closely monitor the subjects for physiological change.

Cost: $13.6 million

Energy Balance Consortium Study

Purpose: Monitoring energy expenditure and appetite

Time frame: September 2013 to December 2014

Participants: 17 overweight and obese males, ages 18 to 50

Question: Does altering carbs and fat in the diet affect calories burned or cause hormonal changes?

Procedure: After four weeks of a standard diet designed to maintain weight, subjects make a drastic switch to a ketogenic diet (5 percent carbs, 80 percent fat) with the same number of calories. If Taubes' hypothesis holds, the change in diet should reduce fat mass and be accompanied by increased energy output.

Cost: $5 million

Stanford University Study

Purpose: Testing diets in the real world

Time frame: March 2013 to December 2016

Participants: 600 overweight and obese subjects, ages 18 to 50

Question: What effect do low-carb and low-fat diets, along with genetic and clinical differences, have on weight loss?

Procedure: In a large so-called free-living study, participants are put on either an extremely low-fat or low-carb diet but are allowed to eat as much protein (and carbs or fat, respectively) as desired. To track daily routines over 12 months, NuSI is developing a smartphone app to monitor eating habits and compliance.

Cost: $7.4 million