PHILADELPHIA — Richard Wrangham, a primate expert at Harvard University, discovered an interesting thing when he tried to eat like the chimpanzees he was studying.
Their raw diet was deeply unsatisfying. He was so hungry he had to return to human foods.
The experience led him to propose that cooked food played a pivotal role in human evolution, helping us diverge from other primates. He theorized that humans -- the only animals that can't live on a raw, wild diet -- could extract more usable energy from cooked foods because they were easier to digest. That would have allowed us to feed bigger brains. Also, chimpanzees spend six or seven hours a day chewing, so we were able to do more civilized things with our time.
His hypothesis is still under debate, but Rachel Carmody, who was a researcher in his lab, lent support with a finding that lab mice did indeed become heavier on cooked than on raw food although they took in the same number of calories.
Separately, a study by the U.S. Department of Agriculture last year found that the typical calorie-measuring technique overestimates how many calories people get from an ounce of almonds, which are difficult to digest. Instead of 170 calories, they concluded, the nuts have 129.
These are among many new lines of research that call into question our long-standing comprehension of food energy. Calories are starting to look a lot more complicated. Some of us — we won't say who — have figured that 500 calories of cake were the same as 500 calories of cauliflower when it came to dieting (not nutrition). We may have to rethink.
"A calorie is a calorie from an energy balance point of view, but, from an effect on the body, there may be a difference," said Dale Schoeller, a professor of nutritional sciences at the University of Wisconsin and an officer of the Obesity Society.
Researchers like Carmody question whether the calories you see on food labels accurately reflect how many calories your body actually uses. Others are studying the complex chain of signals that foods trigger, telling the brain you're hungry or full or need to store fat. The calories may be the same, but some foods, like cake, make not eating more difficult.
It might also matter whether you eat at night or in the morning. A University of Pennsylvania study last year found that mice that ate when they ordinarily would have been sleeping gained more weight than mice that ate at the regular time. An Israeli study published recently in the journal Obesity found that overweight women lost more weight when breakfast, rather than dinner, was their biggest meal of the day, even when the day's total calories were the same.
Then there's the effect of the 2 to 4 pounds of microbes that live in our guts. They also use the food we eat and send signals to our brains. A recent study compared what happened when mice raised in a sterile environment were given transplants of gut bacteria from obese and thin humans. Those who got microbes from heavy people gained more weight.
And we don't all burn calories at the same rate. A thousand calories don't have the same effect in a guy who has always been thin as in one who just lost 100 pounds. Life's not fair. Once a body establishes what Michael Schwartz, an endocrinologist at the University of Washington, calls a "defended body weight" at an obese level, it's a lot like a set point, and the body fights to maintain it.
Last year, Eric Ravussin, director of the Nutrition Obesity Research Center at the Pennington Biomedical Research Center in Louisiana, helped study contestants from The Biggest Loser who had lost an average of 120 pounds. Even with vigorous exercise, which should maintain muscle mass and rev up metabolism, their metabolic rates had slowed. Ravussin said they needed to take in about 500 fewer calories a day to maintain their weights than someone of the same weight who had not dieted.
"We have to start thinking that calories are not everything," said Lee Kaplan, director of the Obesity, Metabolism and Nutrition Institute at Massachusetts General Hospital.
All of this is slowly shedding light on the nation's obesity epidemic. But there are no simple answers as science progresses in its maddening, inconsistent way. Earlier studies found that people fed diets with the same calories but different types of food lost the same amount of weight.
"It's complex inside of you. It's complex outside of you," said Robert Post, who leads the U.S. Department of Agriculture's Center for Nutrition Policy and Promotion.
He said the USDA, which reports the caloric values of foods, still believes a gram of carbohydrates or protein has four calories whether the food is cooked or raw.
Carmody disagrees. She fed lab mice raw and cooked organic sweet potatoes or beef. They maintained their weight on cooked sweet potatoes, but lost on the raw. They lost about twice as much weight on raw meat as on cooked. Carmody, who is now at Harvard University, studying gut bacteria, said cooking increased the effective caloric value of the meat by 10 percent to 15 percent and the potatoes by 30 percent.
Kaplan suggests another explanation. It's not just how many calories we eat. It's also how many we use. Foods may change that. "They may not have gotten more energy," he said. "They may have burned more energy."
Carmody doesn't recommend an all-raw diet — it's not healthy — but says eating more raw food could help. She agrees with most weight experts that the real drivers of obesity are too much food and too little exercise.
The Nutrition Science Initiative, a nonprofit whose goal is to improve obesity science, has just begun a study it hopes will add more facts — from humans, not mice — to the debate. One huge problem with diet studies involving people is that dieters cheat. This 11-week study will work with inpatients. They'll be fed a standard (healthy) American diet of 35 percent fat, 50 percent carbs, and 15 percent protein or a ketogenic diet consisting of 5 percent carbohydrate, 15 percent protein and 80 percent fat, said Ravussin, one of the investigators.
The overweight participants will be fed enough calories to theoretically keep their weight stable. Researchers will then measure what happens to their weight, metabolism and gut bacteria.
Marion Nestle, a nutrition professor at New York University and author of "Why Calories Count," is looking forward to the results.
In the meantime, she and other experts said, it's still a safe bet people will lose weight if they eat fewer calories than their body needs to maintain its weight. For most overweight people, the standard advice — eat less, exercise more — still makes sense.
"It works every time," Nestle said.
She agrees that calorie measurement is inaccurate. Instead of calorie counting, she recommends weighing yourself regularly. If you're gaining weight, you're eating too much.
Charlene Compher, a Penn nutrition professor, thinks whatever may be wrong with the way we count calories pales in comparison with errors in portion size.
She still thinks there's value in using numbers that help us see the relative energy content of foods. "I feel like at least having a sense of what kind of foods are loaded, if you will, is important information for me to have," she said.