The ‘Geometric Framework’ (GF: a nutritional modelling platform) has revealed that ‘low protein-high carbohydrate’ (LPHC) diets generate the best metabolic health and lifespan in mice. Starch (polysaccharide of glucose) and sucrose (glucose+fructose disaccharide) are the major dietary carbohydrates. We evaluated if the benefits of LPHC diets depend on the type of carbohydrate and dietary protein/fat content.
Male mice (n=500) were fed ad-libitum for 18 weeks one of 30 isocaloric diets with low (10/70), medium (20/60) or high (30/50) protein:carbohydrate energy (fat fixed at 20%) or similarly low, medium or high fat:carbohydrate energy (20% protein). Dietary carbohydrate was sourced from fructose or glucose or their combinations (glucose:fructose 100/0, 75/25, 50/50, 25/75, 0/100). GF analysis showed that diets containing a 50/50 combination of glucose and fructose drove the highest energy intake and were most detrimental for metabolic health (increased body weight, adiposity and liver fat, reduced insulin sensitivity and impaired glucose tolerance) and this was worsened by increasing protein ingestion (including elevated plasma triglyceride). Increasing fat intake impaired glucose tolerance, but adiposity was driven mainly by co-ingestion of glucose and fructose.
Next, mice (n=300) were fed one of 15 isocaloric LPHC diets (protein:carbohydrate:- 5/75, 10/70 or 15/65; 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) was adversely affected by increasing protein intake mostly in combination with high starch intake. Replacement of starch with sucrose minimally affected metabolism, producing benefits such as reduced food intake and adiposity. Decreasing the ratio of protein to carbohydrate in the diet increased energy intake and yielded peak FGF21 levels.
Overall, protein was the major determinant of metabolic phenotype, co-ingestion of glucose and fructose was more harmful than either alone, but high sucrose intake did not have adverse consequences in a LPHC dietary setting.