On the ultraprocessed diet, the subjects on average consumed 500 more calories a day and gained two pounds. A possible reason: The participants’ levels of PYY, a hormone that suppresses appetite, were lower on it, while the levels of ghrelin, a hunger-stimulating hormone, were higher. Because the nutrients were constant, the researchers theorize, the processing itself may somehow trigger the hormonal changes. In a paper published in Cell Metabolism in May, they write that “limiting consumption of ultraprocessed food may be an effective strategy for obesity prevention and treatment.”

The results seemed to reinforce a general, even obvious consensus among nutrition researchers — and yet they generated criticism anyway, much of which highlights fundamental challenges in designing dietary experiments. One charge leveled against Hall’s study, for example: It was too short to observe metabolic and behavioral changes that often take place more than two weeks after a new diet is started. But as Hall points out, it would have been hard to recruit people to live longer under such strict conditions. What’s more, outside the lab, subjects often fail to stick to a diet precisely, and their habits are so variable that it can be tricky to tell for sure whether the meal plan in question is having an effect. Yet it’s impossible to say whether a diet that works in the lab will succeed unless you can study it in real life. “I do think there are ways to get accurate data in free-living people,” Dr. Lydia Bazzano, an epidemiologist at the Tulane University School of Public Health and Tropical Medicine, says. “If you can’t, we’re all sunk.”

At stake is the question of how government agencies and other institutions should deploy limited resources to address a catastrophic national health problem. How should dietary research be conducted in order to ultimately produce results that will be most useful to the public? For instance, most clinical trials are set up, as Hall’s was, to answer an either-or question — say, “Does this diet cause weight loss?” — traditionally by comparing an experimental group with a control. But in nutrition, the answer is often “it depends.” To try to understand how multiple factors might influence a diet’s success, Mayer-Davis and others are working on sequential, multiple assignment, randomized trials (SMARTs), whose subjects, in her words, “move from one treatment to another one to another one over time, depending on how they’re doing.” In a continuing 10-month N.I.H.-funded pilot study, one of the first to use this method to assess dietary strategies, she and colleagues randomly assigned volunteers between 19 and 30 with Type 1 diabetes who are overweight to one of three diets: a low-fat plan or a low-carbohydrate plan, both of which were low in calories, or a Mediterranean-style plan. At three and six months, if they don’t like the diet, haven’t lost 2 percent body weight from their last check-in or are having trouble maintaining their blood-sugar levels, they will move to a different plan. Afterward, statistical analyses will determine what characteristics, including those related to lifestyle, were associated with success, or a lack thereof, for each treatment. Eventually, researchers hope, that sort of information will allow clinicians or even a smartphone app to create a personalized diet.

Of course, even personalized diets would still need to be adhered to, and this raises another quandary. “Fundamentally, especially in the Western world, our diet is fairly unhealthy,” Corby Martin of the Pennington Biomedical Research Center, at Louisiana State University, says. “With really broad strokes we could improve our health by making modifications to our diet that everyone could make.” So why haven’t we? And what are we more likely to follow: a diet that is more personalized than past ones have been or, as in Hall’s formulation, more general?