strong inverse relationship between consumption of ultra‐processed foods and the overall proportion of dietary protein, with mean protein content falling from 18.2 to 13.3% between the lowest and highest quintiles of the dietary contribution of ultra‐processed foods. This occurred because ultra‐processed foods tend to be lower in percent protein and higher in energy from fats and carbohydrates than less highly processed foods. As predicted by protein leverage, a rise in total energy intake was associated with the fall in percent protein as the dietary contribution of ultra‐processed foods increased, whereas absolute protein intake remained near‐constant. Recently, Hall et al. [60] showed similar evidence for prioritization of protein intake in an inpatient randomized controlled trial.
Although more research is needed, existing evidence thus suggests that the strong human protein appetite might interact with the proliferation of ultra‐processed foods in industrialized food environments to generate excess energy intake and obesity. This is a fundamental paradigm shift – it suggests that humans over‐eat fats and carbohydrates (and total energy) not because they have particularly strong appetites for those macronutrients, but because their appetite for protein is stronger than the appetites for fats and carbohydrates. This shift in framing could have a significant impact on obesity research, prevention, and management.
For example, much has been written on the fact that the reduction in fat intake associated with US dietary guidelines failed to stem the rise of obesity. This fact is significant not only because it reflects a failed public health initiative, but it might well have exacerbated the US dietary crisis by ostensibly vindicating dietary fats and demonizing carbohydrates [100–102]. The resulting “macronutrient wars” [103] have further polarized scientific and public debate, diverting attention away from the rational question of “what diet is healthy overall?” towards extreme dietary philosophies focussed around minimizing or excluding a particular macronutrient. Viewed from the perspective of protein leverage, however, a likely reason that reducing dietary fat did not solve the obesity problem is that human appetite systems ensured it was replaced by carbohydrate calories to maintain protein near the target ratio (as in Fig. 6.4). Indeed, amid the ensuing debate around fat vs. carbohydrates, the percentage of energy contributed by protein in the US diet decreased marginally (by 1%), which as noted above, is sufficient to drive an obesity epidemic, and as predicted by the protein leverage hypothesis obesity continued to rise [104].
Figure 6.7 Relationship between ultra‐processed food consumption and protein leverage in the United States. The symbols represent protein and non‐protein energy intakes for the lowest (green) to highest (red) quintiles of ultra‐processed food (UPF) consumption reported in the National Health and Nutrition Examination Survey 2009–2010. Numbers in the legend show the mean dietary contribution of UPF (% of total energy intake) for each quintile. The negatively sloped diagonals represent daily total energy intakes (calculated as the sum of X + Y), and the positive radials represent the dietary protein: non‐protein energy ratio (X/Y). The dark vertical, horizontal, and diagonal lines represent alternative models of macronutrient regulation (as in Fig. 6.1c). As predicted by the protein leverage hypothesis, increasing UPF in the diet was associated with decreased percent dietary protein (18.3–13.3%) and increased total energy intake (8.2–8.9 MJ), while absolute protein intake varied little.
Source: From Martínez Steele et al. [68].
Another example where protein leverage can potentially resolve unexplained phenomena, concerns the fact that the higher the target level for protein intake the more susceptible an individual would be to energy over‐consumption on an obesogenic diet [53] (Fig. 6.6). This could explain the high susceptibility to obesity of populations or individuals with a history of high protein diets. For example, the islandic populations of Oceania, which have until recently remained on marine‐based diets rather than having shifted to carbohydrate‐rich dietary patterns associated with terrestrial agriculture, are among the most susceptible populations globally to obesity and associated disease [105], and the same is true of the circumpolar Inuit [106]. Likewise, individuals who, as infants, were fed milk formulas with protein content higher than human breast milk have increased susceptibility to obesity later in life [70]. Since formula‐fed infants cannot regulate the ingested balance of their diet, it is likely that they compensate post‐ingestively by reducing amino acid retention through upregulating gluconeogenic pathways. If elevated gluconeogenesis is retained into later life – i.e. is developmentally programmed – this would have the effect of increasing the protein target to compensate for reduced protein efficiency hence predisposing to obesity. Finally, muscle protein catabolism and hepatic gluconeogenesis are inhibited by insulin, and this inhibition is impaired in insulin resistance and when there are high levels of circulating free fatty acids. Obesity might thus itself predispose to excess energy intake via increased breakdown of muscle protein and hepatic gluconeogenesis, driving an increased protein intake target [53].
Perhaps most important of all, as discussed next, protein leverage could provide a biologically grounded framework for focussing research aimed at unraveling the complex interactions between humans and food environments.
Why do humans select low‐protein foods that cause energy over‐consumption?
The protein leverage hypothesis simplifies the challenge of understanding how humans interact with food environments by explicitly distinguishing the two primary components of feeding regulation, which foods are selected and how much of each is eaten. Protein leverage addresses the second of these questions through attributing the over‐consumption of energy on low protein diets, such as those rich in ultra‐processed foods, to the strong human appetite for protein. In so doing, it highlights the importance for public health research of addressing the questions of why humans choose to eat low‐protein ultra‐processed foods that dilute protein resulting in excess energy consumption and how this can be managed. These questions, we believe, are the highest priority, both for understanding better how people interact with transitioning food environments to shape their diets and for formulating policy and other interventions to influence these interactions.
There are many contributing factors. Important among these is that the industrial synthesis of edible products from highly refined ingredients, as in ultra‐processed foods, offers opportunities for customizing compositions in ways specifically designed to encourage consumption. One method is combining ingredients in ratios that are hyperpalatable, to dial in a “bliss point” that maximizes hedonic responses. This can be done, for example, by including carbohydrates and fats in ratios that are highly palatable, and intensifying the effect by increasing the concentration of the mixture through minimizing other components such as protein and fiber. Palatability can be further enhanced by adding salt or other flavor‐enhancers.
Some of these manipulations not only target the food choice component of diet regulation, but also influence or interact with the amounts eaten. For example, high palatability can itself stimulate appetite and delay satiety [107]. Increasing the ratio of fats and carbohydrates to protein to increase palatability will also result in increased consumption via protein leverage, an effect that will be exacerbated when the other major satiating dietary component, fiber, is also low [62]. Using a formula that integrates the protein, fiber, fat, and energy density of foods to calculate satiety potential, Fardet et al. [108] showed that ultra‐processed foods are significantly less satiating than other foods.
A particularly insidious processing strategy is to impart a savory flavor on low‐protein foods. In humans, like other species, an important mechanism for nutrient balancing
