Five years ago, University of Washington endocrinologist Scott Weigle, MD, got a call from Germany. A young researcher there named Mario Kratz was looking for a way to test an interesting hypothesis. Kratz had been studying omega-3 fatty acids, a complex group of chemicals often found in fish oil and thought to have a wide range of health benefits. He knew that when researchers fed mice lots of omega-3s, the rodents lost weight. He wondered whether the same tactic would work for humans—and if so, why. Weigle was intrigued. “We felt there was a very good reason to believe that diets high in omega-3 might lead to weight loss in humans,” Weigle says. “There was a very nice study in mice that suggested that was true.”
For people with diabetes, the animal studies held tremendous promise. The studies centered on a hormone called leptin produced in the body’s fatty tissue. “Its major function is to signal to the brain that fat stores are abundant,” Kratz says. Lots of fat means lots of leptin, which in turn sends the brain a signal to stop storing fat and start burning more calories. In fact, some scientists have suggested that obesity may be a case of leptin resistance—the brain simply missing the red light that says enough is enough.
With the help of an ADA grant, Weigle invited Kratz to join his Seattle lab. In 2004, the two researchers set out on what became a four-year odyssey to precisely measure the effects of omega-3 fatty acids in humans. “We figured if we gave them a diet rich in omega-3, maybe they would become more leptin sensitive, and that would make them lose weight over time,” Kratz says. “If the effects of omega-3 fatty acids on mice could be translated to people, the public health impact would be huge.”
To test their hunch, the two researchers identified 26 subjects who were overweight but otherwise healthy and divided them into two groups. For 16 weeks, the study participants were given all their meals—breakfast, lunch, dinner, and a snack—by the research team. (Four months of free food cooked by professional dietitians was a definite draw when it came to recruiting study participants, Weigle says.) The menus looked the same and had the exact same number of calories, but half the subjects were unknowingly given meals extremely high in omega-3 fatty acids.
The study was a tremendous logistical challenge. Participants came to the University of Washington twice a week to pick up their food. Whatever they didn’t eat was returned to the clinic, where technicians weighed it so their exact calorie consumption could be measured. Every gram was precisely calculated: Weigle had dietary technicians at the University of Washington use scissors to trim tortillas to within a half-gram, or hundredth of an ounce, of the correct weight.
The study was “blind” in that each group had to be kept in the dark about whether or not they were getting the omega-3 rich diet. Since everyone was fed the same menu—a typical dinner might consist of turkey lasagna and grapes or pizza with pesto—Weigle and Kratz had to be creative about slipping omega-3s into half the meals. They had specially made omega-3-rich margarine and placebo vitamin capsules with no omega-3s. “It took almost a year to get all the foods right,” Weigle says. The team had to rent a warehouse freezer in Seattle to store all the food.
The study ran for almost two years. The results were a lesson in the ups and downs of science: After all that work, the researchers discovered their initial hypothesis was wrong. The group that ate lots of omega-3 fatty acids during the 16-week study didn’t lose more weight than the control group, and the levels of leptin in their blood were roughly the same. “It was a reasonable hypothesis that if we gave people omega-3 they would lose weight,” Weigle says. “That turns out not to be true.”
But the study may yet bear fruit. So far, the researchers have used the samples to look at leptin levels as well as the effects of omega-3s on another hormone produced in the body’s fatty tissue called adiponectin. But with freezers full of blood, urine, and tissue samples collected over the 16 weeks of the study, Weigle and Kratz—whose work helped him land a job at Seattle’s Fred Hutchinson Cancer Research Center—have a resource for future investigations into the effects of omega-3s elsewhere in the body. Says Weigle: “Having a well-controlled sample set like this is like having money in the bank.”