Abstract
A significant contributor to the rising rates of human obesity is an increase in energy intake. The ‘protein leverage hypothesis’ proposes that a dominant appetite for protein in conjunction with a decline in the ratio of protein to fat and carbohydrate in the diet drives excess energy intake and could therefore promote the development of obesity. Our aim was to test the ‘protein leverage hypothesis’ in lean humans by disguising the macronutrient composition of foods offered to subjects under ad libitum feeding conditions. Energy intakes and hunger ratings were measured for 22 lean subjects studied over three 4-day periods of in-house dietary manipulation. Subjects were restricted to fixed menus in random order comprising 28 foods designed to be similar in palatability, availability, variety and sensory quality and providing 10%, 15% or 25% energy as protein. Nutrient and energy intake was calculated as the product of the amount of each food eaten and its composition. Lowering the percent protein of the diet from 15% to 10% resulted in higher (+12±4.5%, p = 0.02) total energy intake, predominantly from savoury-flavoured foods available between meals. This increased energy intake was not sufficient to maintain protein intake constant, indicating that protein leverage is incomplete. Urinary urea on the 10% and 15% protein diets did not differ statistically, nor did they differ from habitual values prior to the study. In contrast, increasing protein from 15% to 25% did not alter energy intake. On the fourth day of the trial, however, there was a greater increase in the hunger score between 1–2 h after the 10% protein breakfast versus the 25% protein breakfast (1.6±0.4 vs 25%: 0.5±0.3, p = 0.005). In our study population a change in the nutritional environment that dilutes dietary protein with carbohydrate and fat promotes overconsumption, enhancing the risk for potential weight gain.
Highlights
Increased energy intake is a significant contributor to the rising rates of human obesity [1] and an important priority is to understand the factors underlying this shift
It has been proposed that a change in the ratio of protein to fat and carbohydrate in the diet may play a central role in increased energy intake – the ‘protein leverage hypothesis’ (PLH) [2,3]
That subjects were close to metabolic equilibrium was indicated by estimated habitual protein intakes being similar to protein intakes during the 10% and 15% treatment periods: there was no difference in total urinary urea excretion prior to and following the 10% (p = 0.1) and 15% (p = 0.6) protein study periods (Figure S2)
Summary
Increased energy intake is a significant contributor to the rising rates of human obesity [1] and an important priority is to understand the factors underlying this shift. The role of dietary protein in the emerging obesity epidemic has, until recently largely been ignored This is partly because protein provides only a minor component of the dietary energy for humans (typically around 15%) and because its intake has remained far more constant over time and across populations than either fat or carbohydrate [2,4]. Experimental data suggest that the response of humans when faced with imbalanced diets is to prioritize the absolute intake of protein to a ‘target’ level at the expense of regulating fat and carbohydrate intake [2,3,6,7] Such ‘protein leverage’ [2] has been demonstrated in numerous other species, including non-human primates [8], pigs [9,10], rodents [10,11], birds [12], fish [13] and insects [14]. The most extreme example of protein leverage reported to date comes from freeranging spider monkeys [8], in which protein intake was maintained constant across a wide range of % protein diets; whereas in mice protein compensation is partial due to counterbalancing feedbacks from carbohydrate [11]
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