total energy intake is maintained constant with variation in dietary macronutrient ratios [33].
Figure 6.3 Regulatory responses by free‐ranging Peruvian spider monkeys (Ateles chamek) to ecologically imposed variation in dietary macronutrient ratios. Each point represents the daily protein and non‐protein energy intake of an individual. The overall pattern of intakes suggests protein prioritization, in which the target intake of protein is maintained, and fat and carbohydrate intake vary with daily variation in dietary macronutrient balance (blue pattern in Fig. 6.1).
Source: Modified from Felton et al. [34].
Human macronutrient regulation
Across the many species studied using nutritional geometry, one thing that stands out is the power of macronutrients. Once appetite responses have been mapped to variation in dietary protein:carbohydrate:fat mixture, including intake targets and responses to constrained imbalance, an animal’s behavior, health, and life history (for example reproduction and longevity) can be predicted and manipulated with a high degree of certainty. Of course, micronutrients also play an important role in biology, and for some, notably calcium [38] and sodium [39], specific appetites have been identified. However, they seldom, if at all, have the same leverage over the animal’s interactions with its environment as do macronutrients. This suggests that evolution has converged on low‐dimensional ingestive regulatory systems, and relatively simple models can go a long way towards understanding key aspects of nutrition [19].
Can obesity be understood within this framework? A first step towards empirically addressing this question is to determine whether the kinds of regulatory responses recorded in insects and wild primates also exist for our species.
Do humans select an intake target?
Several lines of evidence, spanning global patterns of macronutrient intake distributions, experimental trials, and mechanistic studies, indicate that humans have the capacity to regulate the intake of macronutrients to an intake target as do other species.
Lieberman et al. [40] analyzed dietary macronutrient distributions from national survey data, including the US National Health and Nutrition Examination Survey (NHANES), and data from 13 countries with gross domestic products above $10,000 per capita per annum. The proportion of protein in the diets of all 14 countries was highly consistent at 16% of total energy, whereas calories from fat and carbohydrates were substantially more variable within and between populations. In the United States, protein, fat, and carbohydrate comprised 16, 33, and 48% of total energy intake, respectively.
Fat and carbohydrate varied significantly with age and race, but protein intake was not significantly related to demographic or lifestyle factors. These results support previous reports [e.g. 13,41] showing consistency across countries, populations, and time (Fig. 6.4a) of protein intake at ~15% of total energy, whereas fat and carbohydrate distributions vary more widely. Such consistency for protein is suggestive of regulation of the ratio of protein to non‐protein energy (fats and carbohydrates) in the diet.
Experimental studies have provided evidence for balancing macronutrient intakes in human subjects, with protein intake being especially closely regulated [e.g. 42–44]. Campbell et al. [45] allowed 63 subjects to freely compose a diet from foods containing 10, 15, and 25% protein for 3 days (Fig. 6.4b). Subjects closely tracked a mean 14.7% protein intake, which differed highly statistically significantly from the null expectation of no selection (16.7%). It is significant that the target intakes suggested by population studies and experimental studies converge within a narrow margin of 15–17%. Interestingly, this is not dissimilar for non‐human apes studied in the wild, which range between 10% (orangutan) and 20% (mountain gorilla), with our closest living relative, the chimpanzee, selecting a diet of 13% protein [35].
At a physiological level, there have been significant advances in understanding the mechanisms controlling macronutrient appetites [46]. Most notable has been the discovery that fibroblast growth factor (FGF)‐21 is the circulating signal of low‐protein status in humans and rodents. FGF‐21 is produced mainly in the liver and acts in the brain to stimulate protein appetite, guiding mice either to select protein‐rich foods if available or to increase intake of low‐protein diets to ensure increased protein intake, with associated increased energy intake on low‐protein, high‐energy diets [47,48]. FGF‐21 is also implicated in the inhibition of carbohydrate intake under low‐protein, high‐carbohydrate feeding in mice and humans [49–52].
Response to variation in dietary macronutrient balance: protein leverage
The fact that dietary percent protein is far more consistent across populations than fats and carbohydrates [e.g. 40] suggests that humans, like most other primate species studied to date, regulate protein intake more strongly than either fat or carbohydrate. An important question is how the strong appetite for protein interacts with the appetites for fat and carbohydrate in the face of variation in dietary macronutrient balance. Testing this interaction requires examining how the absolute amounts of macronutrients eaten vary with variations in dietary macronutrient ratios.
Figure 6.4 Dietary macronutrient regulation in humans. (a) Data from the FAOSTAT global nutrient supply database for the United States indicate that compared with fat and carbohydrate, which have increased since 1960, protein supply has remained stable, as expected if humans regulated protein intake most strongly. (b) Daily protein vs. non‐protein energy intake by 63 adult Jamaican volunteers, averaged for each subject over the 3‐day experimental period clustered tightly around a dietary macronutrient ratio of 14.7% energy from protein. Red symbols are females and blue symbols males. The solid radial lines are nutritional rails representing the composition of the three experimental menus from which the diets could be freely selected (10, 15, and 25% protein by energy). The shaded region represents the range of diets that could potentially be selected from these menus, and the dashed line represents the expected outcome if the subjects mixed the diets randomly (16.7% P). The selected macronutrient ratio was significantly different from the random outcome (P < 0.001).
Source: Adapted from Campbell et al. [45].
Global data from the FOASTAT nutrient supply database for the United States indicate that percent protein in the food supply has fallen by ~1% since 1960 (Fig. 6.5a), and concurrently energy supply has risen (Fig. 6.5b), yet absolute protein supply has stayed remarkably stable (Fig. 6.4a) [53,54]. Hence, paradoxically, although protein has made little direct contribution to excess calorie intake throughout the obesity epidemic, its tight regulation may have played a major role in driving excess calorie intake in the form of fats and carbohydrates.
