The ‘Geometric Framework’ (GF) for nutrition has revealed that ‘low protein-high carbohydrate’ (LPHC) diets generate the best mid-late life cardio-metabolic health and lifespan in mice. Starch (polysaccharide of glucose) and sucrose (disaccharide of glucose+fructose) are the major dietary carbohydrates. We further evaluated if the benefits of LPHC diets depend on the type of carbohydrate and dietary protein content.
Male mice (C57BL/6; n=300) were fed ad-libitum for 18 weeks one of 15 isocaloric diets with low (10/70), medium (20/60) or high (30/50) protein:carbohydrate energy (fat fixed at 20%). These diets provided 30% of carbohydrate energy from starch and remaining 70% from five different monosaccharide glucose-fructose ratios (100/0, 75/25, 50/50, 25/75, 0/100). GF analysis showed that in contrast to their consumption in isolation, a combination of glucose and fructose intake was most detrimental for metabolic health (↑weight, ↑adiposity, ↓insulin sensitivity and ↓glucose tolerance) and this was worsened by increasing protein ingestion.
Next, the metabolic effects of sucrose and starch intake were compared in the specific context of LPHC diets. Mice (n=300) were fed ad-libitum one of 15 isocaloric LPHC diets (protein:carbohydrate:- 5/75, 10/70 or 15/65, and 20% fat). Dietary carbohydrate consisted of five different sucrose-starch ratios (20/80, 35/65, 50/50, 65/35, 80/20). Metabolic status (weight, energy expenditure, adiposity, insulin sensitivity, triglyceridaemia, nutrient signalling, plasma metabolites) was adversely affected by increasing protein intake mostly in combination with high starch intake. Replacement of starch with sucrose minimally affected metabolism, producing some benefits such as reduced food intake and adiposity. Decreasing the ratio of protein to carbohydrate in the diet increased energy intake and yielded peak FGF-21 and brown fat levels.
Overall, protein was the major determinant of metabolic phenotype, glucose and fructose intake in combination were more harmful than either alone, but high sucrose intake did not have adverse consequences in a LPHC dietary setting.