Do calories or insulin drive weight gain?

Nobody in the debate disputes the arithmetic: as Kevin Hall of the US National Institutes of Health puts it, weight changes are accompanied by imbalances between calorie intake and expenditure. The quarrel is over what causes the imbalance, and it is unresolved. Hall and colleagues defend the energy balance model, which puts the brain at the centre, regulating food intake mostly below conscious awareness in response to the body's energy needs and its surroundings. David Ludwig and colleagues defend the carbohydrate-insulin model (CIM): hormonal responses to highly processed carbohydrates push calories into fat tissue, leaving fewer for the body's needs, so that growing fat stores drive people to overeat to compensate.

The two views make different predictions. On the CIM, swapping carbohydrate for fat at equal calories should raise energy expenditure and fat loss; a view that a calorie is a calorie predicts no important difference. Hall's team tested this on a hospital ward in a study that the Nutrition Science Initiative, a group set up to validate the carbohydrate-insulin hypothesis, convened and partly funded. Seventeen overweight or obese men were switched from a high-carbohydrate diet to an isocaloric ketogenic one. Fat loss did not speed up, and energy expenditure rose only slightly, near the limits of detection. In 2017 Hall wrote that the hypothesis had been falsified by experiment.

Its defenders disagree. Ludwig and Cara Ebbeling argue that feeding studies have lacked the rigour and duration to test the model, and a secondary analysis of the same data, led by Mark Friedman of the Nutrition Science Initiative, found a substantial rise in energy expenditure, though apparently only on days spent on the ward outside the metabolic chamber.

One point of overlap comes from the CIM side. Ludwig's group wrote in 2022 that public health action need not await the end of the debate, as both models target processed carbohydrates as major drivers of obesity.