Cardio-metabolic consequences of dietary carbohydrates: reconciling contradictions using nutritional geometry

Carbohydrates are the major source of dietary energy, but their role in health and disease remains controversial. Recent epidemiological evidence suggests that the increased consumption of carbohydrates is associated with obesity and increased risk of mortality and dietary trials show that carbohydrate restriction leads to weight loss and improved glycaemic status in obese and diabetic subjects. In contrast, the diets of populations with long and healthy lifespans (e.g. traditional Okinawans from Japan) are high in carbohydrate and low in protein, and several clinical and preclinical studies have linked low-carbohydrate-high-protein diets with increased mortality risk. In this paper we attempt to reconcile these contradictory findings by moving beyond traditional single-nutrient analyses to consider the interactions between nutrients on health outcomes. We do so using the Geometric Framework (GF), a nutritional modelling platform that explicitly considers the main and interactive effects of multiple nutrients on phenotypic characteristics. Analysis of human data by GF shows that weight loss and improved cardio-metabolic outcomes under carbohydrate restriction derive at least in part from reduced caloric intake due to the concomitantly increased proportion of protein in the diet. This is because, as in many animals, a specific appetite for protein is a major driver of food intake in humans. Conversely, dilution of protein in the diet leverages excess food intake through compensatory feeding for protein ('protein leverage'). When protein is diluted in the diet by readily digestible carbohydrates and fats, as is the case in modern ultra-processed foods, protein leverage results in excess calorie intake, leading to rising levels of obesity and metabolic disease. However, when protein is diluted in the diet by increased quantities of less readily digestible forms of carbohydrate and fibre, energy balance is maintained and health benefits accrue, especially during middle age and early late-life. We argue that other controversies in carbohydrate research can be resolved using the GF methodology in dietary studies.