Testing Protein Leverage in Lean Humans: A Randomised Controlled Experimental Study

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.

The nature of nutrition: a unifying framework

“…The resulting intake array was thus a vertical line, with little variation on the protein axis compared with the axis for non-protein. This is very similar to the rule of compromise that has been observed in experimental studies of humans Gosby et al 2011), which appear to be an important contributory factor to the epidemic of obesity that has swept many countries in recent decades.…”

0476 Low protein diets produce divergent effects on energy balance

“…The hypophagic effect of protein-free diets, and hyperphagic effect of very low protein and moderately low protein diets, in the current study are consistent with the 'protein leverage' hypothesis 2 , as well as previous studies on protein restriction in rats, mice and humans 1,[6][7][8][9]14,17,22 . Although the low protein-induced hyperphagia is associated with a central orexigenic drive 11,[15][16][17][18] , the peripheral signals that transmit information to central neural networks are poorly defined.…”

“…A corollary to this hypothesis is that a reduction in the dietary protein concentration would increase total energy intake, due to overconsumption of carbohydrates and fat, in an effort to meet protein requirements. Consistent with this, moderately protein deficient diets were found to produce hyperphagia in rodents [6][7][8][9] and in some 1,10,11 but not all human studies 12,13 , whereas, severe protein restriction below a certain threshold leads to a reduction in food intake in rodents 9,14 . However, little is known of the underlying mechanisms by which moderate protein deficiency elicits such behavioural and metabolic adaptations and promotes positive energy balance with consequent predisposition to obesity and other metabolic disorders.…”

“…The 'protein leverage' hypothesis posits that protein intake is tightly regulated in several species including rats, mice and humans, which consume to acquire their required protein rather than meet requirements for fats and carbohydrates [1][2][3] . An increase in dietary protein density would decrease intake of carbohydrates and fats with consequent reduction in energy intake.…”

Impact of Diet Composition on Blood Glucose Regulation

“…Satiating effects of dietary protein, a reduced choice of foods, and an aversion against dietary fat in the absence of carbohydrates have all been attributed to better weight loss with high protein diets (Weickert et al, 2005). Lowering the percent protein of the diet from 15% to 10% increases total energy intake (Gosby et al, 2011), further indicating that a higher intake of dietary protein may help to reduce energy intake. In a recent review, it is concluded that dietary protein by acting on satiety and energy expenditure in negative energy balance may prevent weight cycling effects (Westerterp-Plantenga et al, 2012), indicating a beneficial role on weight regulation.…”