Two British researchers, Prof. Alan Kekwick and Dr. Gaston L.S. Pawan, did the groundbreaking research on the metabolic advantage. In the 1950s and 1960s the two were at the top echelon of British obesity research, both serving as chairmen of many international conferences.
In the early 1950s the two researchers were struck by the many studies that suggested that diets of different compositions of fat, protein and carbohydrate provided differing rates of weight loss.
Their subsequent study on obese subjects found that those on a 1,000-calorie diet comprised of 90 percent protein and especially those on a diet comprised of 90 percent fat lost weight (0.6 pounds and 0.9 pounds per day, respectively). However, when the same subjects were given a diet with the same number of calories, but comprised of 90 percent carbohydrate, they did not lose any weight in fact, they gained a little.
Kekwick and Pawan then replicated a study with humans that they had previously done on animals and found the same phenomenon: A diet of 1,000 calories worked well for weight loss as long as carbohydrate intake was low, while a high-carbohydrate 1,000-calorie regimen took off very little weight. They then showed that their subjects did not lose at all on a so-called balanced diet of 2,000 calories. But when their diet contained primarily fat and very little carbohydrate, these same obese subjects could lose weight even when they ate as many as 2,600 calories a day. The difference is that weight loss between the two programs comes close to being a pound per day. Despite the Middlesex doctors impeccable reputations, the majority of their colleagues remained skeptical, given their calorie-is-a-calorie mind-set. They set out to disprove this intellectual bombshell that Kekwick and Pawan had dropped on them.
Kekwick and Pawan conducted water-balance studies that showed water loss to be only a small part of the total weight lost. Kekwick and Pawan then embarked on a two-year study of mice in a metabolic chamber. By measuring the loss of carbon in the feces and urine, they were able to show that the mice on the high-fat diet excreted considerable unused calories in the form of ketone bodies, as well as citric, lactic and pyruvic acids. At the end of the study period, they analyzed the fat content of the animals bodies and found significantly less fat on the carcasses of the mice that had been fed a high-fat, controlled carbohydrate diet.