The FB4 Study and Weight Loss

For many, the journey from normal life to a stint living with strangers in a secluded conference center began with a Facebook ad. "JOIN OUR WEIGHT LOSS DIET STUDY!" it beckoned. "Lose 15% of your weight and stay for 3 months at a wooded lakefront retreat in Massachusetts."

"I thought it was fake," says Charisse Shields, a 33-year-old actress, recalling the promised perks: "free housing, gourmet meals and up to $10,000." But she discovered the study was, in fact, entirely legit and being led by prominent researchers at Boston Children's Hospital and Indiana University--Bloomington. By late April 2019, she and 12 fellow participants in the ambitious "FB4" study were preparing to leave the cocoon of the Warren Conference Center and Inn, where they'd spent the previous 13 weeks eating every morsel on their carefully calibrated plates in an attempt to answer a fundamental question in the science of weight loss: Which diet helps keep the pounds off?

"Many people can lose weight over the short term," says FB4 study director Cara Ebbeling, co-director of the Boston Children's obesity prevention center. What's tough is maintaining that loss over time. So before ever checking into the Inn, Shields and the others had to gradually lose at least 12% of their body weight, over about three months, by eating prepackaged, very-low-carb meals that the researchers provided. For Shields, this involved dodging abundant free food on a job site, where she became known as the lady who toted her study grub around in search of a microwave.

Restrictive diets are no picnic. Compounding matters: Once people lose weight, they burn fewer calories -- a physiological slump that can undermine even valiant efforts. Thus the weight-maintenance focus of the roughly $13 million study, which is enrolling adults nationwide who are at least moderately overweight. Specifically, it's examining whether what people eat vs. simply how many calories impacts metabolism and body fat. Is there a sweet-spot ratio of carbs, protein and fat that can help prevent weight regain, when the body seems wired to self-sabotage?

[See: The 10 Best Diets for Healthy Eating.]

When FB4 participants first arrive, they're assessed to estimate how many daily calories their newly slimmed bodies burn. Then they're randomly assigned to one of three diets with individualized calorie counts based on those measurements: very-low-carb; high-carb with some added sugar; and high-carb with no added sugar. The two high-carb variations are designed to tease out whether sugar is uniquely harmful to weight control, says pediatric endocrinologist Dr. David Ludwig, co-director of BCH's obesity prevention center and an FB4 principal investigator.

No crumbs left behind. Serving three meals a day that conform to the prescribed diets, with quantities painstakingly calculated to match each person's specific caloric burn rate, that taste good -- and that provide variety enough to avert deadly boredom -- wasn't what the resort's staff was used to. "We're a hospitality company," says Warren Conference Center and Inn General Manager Kim Sternick. But FB4 requires measuring ingredients down to at least the gram. Each meal is built around common elements, then tweaked to meet the diets' stringent requirements. Consider a taco-themed lunch: The very-low-carb group gets 80% lean ground beef with a romaine lettuce wrap, steamed cauliflower and walnuts; the high-carb, high-starch group gets a soft taco with 90% lean beef, tortilla chips, cauliflower with farro and raisins; while the high-carb, high-sugar group gets all that -- minus the chips -- plus Kool-Aid and jelly beans.

About those jelly beans: They're actually assorted Jelly Bellys, and no, you can't pick out the flavors you hate, nor can you skip or swap any other component of your meals. Participants are monitored to ensure every crumb -- every drop of sauce -- is scraped off the plate with a spatula and consumed. People with food allergies are excluded from FB4, and unrepentant picky eaters need not apply. Study dietitians did cede to common food aversions, leaving grapefruit, cilantro and mushrooms off the menu. Sanctioned spices -- e.g., curry, paprika, cinnamon and hot pepper sauce -- are available. Coffee is allowed (sweetened only with stevia) but with a daily limit on caffeinated cups. Celebrating a birthday? Expect tea with the flavor of confetti cake. Because exercise also influences calorie burn, everyone must log at least 30 daily minutes (90 max) at a mild to moderate clip. Participants wear an activity tracker, another tracker to gauge sleep and a continuous glucose monitor to measure blood sugar response to meals. In their free time, they work remotely; take classes online; practice hobbies; read. Yoga, career coaching, workshops and other activities are offered. Since FB4 is longer than a typical residential controlled feeding study -- lingo for testing diets under conditions that assure only the prescribed foods are eaten -- organizers take care to make the experience enjoyable. (The $10,000 for finishing the study doesn't hurt.)

A weighty issue. If this all seems over the top, it's because the question of how to handle obesity and its attendant chronic diseases is urgent. The proportion of U.S. adults with obesity has climbed from about 13% in the 1960s to nearly 40%. But precisely why is subject to intense debate. Ludwig and others propose that a longstanding hypothesis known as the carbohydrate-insulin model may explain why simply restricting calories doesn't work for everyone. Here's the idea in a nutshell: When carbs, particularly highly processed ones, hit the bloodstream, they cause a rush of insulin that socks away calories in fat cells, leaving too few for the rest of the body. As a result, a diet heavy on processed carbs makes people hungrier and prone to overeating. And resisting that hunger can slow down metabolism, Ludwig explains.

[See: U.S. News' 41 Best Diets Overall.]

Last fall, Ludwig, Ebbeling and colleagues published results of the Framingham State Food Study, which examined this question under different research conditions; they found that a low-carb diet increased calorie burn among adults trying to maintain weight loss. Other researchers dispute the carbohydrate-insulin model (although they say processed carbs may drive obesity for other reasons). The debate is ongoing, and FB4 stands to contribute. The study is slated to end in 2021, after which data from a planned 125 participants -- who will continue arriving in cohorts -- will be crunched and the results eventually published.

The question of which diet works best is really two different questions, says Tanya Halliday, assistant professor of kinesiology at the University of Utah: "Are we interested in the biology and physiology, or do we mean what diet is best in the current environment that we live in?" FB4 addresses the physiology piece, but not under real-world conditions; then there are studies like DIETFITS, where participants got dietary advice and behavior-change tips over 22 group sessions but were on their own for food shopping, prep and eating. For that trial, researchers randomly assigned 609 adults classified as overweight or obese to either a low-fat or healthy low-carb diet for a year. Neither diet delivered a weight-loss advantage, nor did genetic patterns or insulin resistance, also considered, relate to success.

A real-world problem. This kind of experiment can show how diets do in the real world, where researchers can't really control whether participants follow diets to a T or accurately report what they're eating. Researchers trade off the rigor and tight supervision of controlled feeding studies for the broader applicability of real-world trials, says Christopher Gardner, director of nutrition studies at Stanford Prevention Research Center and lead author of DIETFITS, whose results were published in 2018.

Both study types are necessary. "If we understand the mechanism, we can optimize it," says neuroscience and obesity researcher Stephan Guyenet. "At least in theory, we could design diets that are better than what we currently use." If a certain macronutrient balance emerges as superior, people might be more motivated to change their diets, and you'd have "the basis for more scientifically informed public health advice and policy," Ludwig says.

What's often lost in the diet wars is that individuals are individual -- no one approach will likely work for all. "The diet educators were stunned" in DIETFITS to see how people thrived and failed on completely opposite diets, possibly owing to differences in satiety, Gardner says. That's why two people can eat a cheesy veggie omelet or steel-cut oatmeal with berries and have wholly different responses: immediate fullness or hunger pangs demanding seconds. And countless other factors influence the "ideal" diet -- from taste preferences and cultural traditions to what's easy, affordable and available. A 2014 review published jointly by three major health organizations concluded that as long as people burn off more calories than they take in, weight loss can happen on virtually any diet. The best diet is one that revolves around whole foods and vegetables, while limiting refined grains and sugar. If everyone ate that way, Gardner bets we'd "solve 50%" of the obesity problem.

Regardless of the diet, experts generally agree: It would be great if research could serve up a better recipe for making new habits stick long term. And that's the challenge awaiting FB4 participants, who'll have to maintain their weight loss on their own steam, using new insights coupled with some phone-based nutritional counseling sessions. Charisse Shields now knows she can eat more than she thought, provided her meals are balanced and the food quality, high. Gillian Cotton-Graves, 19, vows to join a gym and eat more mindfully. Carla Zelinksi, 38, will focus on moderate carbs while getting consistent, but not extreme, exercise. Cosetta Medina, 34, no longer craves bread and will aim for nutrient-dense meals. Dan Alban, 23, plans moderation, plus more cauliflower. They say the three-month hiatus from their usual routines to reflect on their dietary habits and life overall has been a "gift." Notes Medina: "I'm so proud of all of us."

[See: The 12 Best Diets for Your Heart.]

For more details or to apply to be part of FB4, visit childrenshospital.org/fb4study.

The Three Diets

The FB4 study looks at whether the balance of nutrients affects metabolism and body fatness. All three study diets get about 20% of their calories from protein.

-- Very-low-carb: About 75% fat, 5% carbs. That means yes to nuts and bacon; no to dinner rolls and pasta.

-- High-carb with some added sugar but no refined grains: About 25% fat, 55% carbs, including veggies and whole grains; about 20% of total calories come from added sugars (such as jelly beans and gummy bears).

-- High-carb with no added sugar and some refined grains: About 25% fat, 55% carbs; about half of grains come from refined sources like crackers and rice cereal.