Dietary Protein to Carbohydrate Ratio and Caloric Restriction: Comparing Metabolic Outcomes in Mice

Abstract

Summary Both caloric restriction (CR) and low protein, high carbohydrate (LPHC) ad libitum-fed diets increase lifespan and improve metabolic parameters such as insulin, glucose and blood lipids. Severe CR, however, is unsustainable for most people; therefore, it is important to determine whether manipulating macronutrient ratios in ad libitum-fed conditions can generate similar health outcomes. We present the results of a short-term (8 week) dietary manipulation on metabolic outcomes in mice. We compared three diets varying in protein to carbohydrate ratio under both CR and ad libitum conditions. Ad libitum LPHC diets delivered similar benefits to CR in terms of levels of insulin, glucose, lipids and HOMA, despite increased energy intake. CR on LPHC diets did not provide additional benefits relative to ad libitum LPHC. We show that LPHC diets under ad libitum-fed conditions generate the metabolic benefits of CR without a 40% reduction in total caloric intake.

A 7-day high protein hypocaloric diet promotes cellular metabolic adaptations and attenuates lean mass loss in healthy males

“…Thus a greater relative change was observed pre-post intervention in the ER groups, but no group interaction was apparent. In mice and subsequent to 8 weeks on a hypocaloric diet a significant reduction in RER was observed compared to relative to energy matched diets [31]. Similar to the results from this study, RER was reduced to the same level in the hypocaloric group's independent of dietary protein intake (5% vs. 33% vs. 60%).…”

“…Similar to the results from this study, RER was reduced to the same level in the hypocaloric group's independent of dietary protein intake (5% vs. 33% vs. 60%). [31] also reported a significant reduction in RER in the eucaloric high protein group relative to the eucaloric high protein diet, however this was not to the amplitude of the any of the hypocaloric diets. This suggests that in an eucaloric state restricted carbohydrate (increased protein intake) results in a reduction in RER, however calorie restriction has a greater metabolic impact, independent on macronutrient ratio.…”

Overexpression of CYB5R3 and NQO1, two NAD+‐producing enzymes, mimics aspects of caloric restriction

“…Conversely, there was clear reduction in key regulators of the lipid oxidation process, including PGC‐1α, SIRT3, ACAA2, and HADHSC in RedTg livers. It has been previously reported that ad libitum‐fed animals on diets that are high in carbohydrates, but low in proteins, have greater adiposity and the longest lifespan (Solon‐Biet et al., 2014), although the association between the intake of protein/carbohydrates and adiposity is still a matter of debate (Fontana et al., 2016; Maida et al., 2016; Solon‐Biet et al., 2015) including prospective cohort studies of humans (Berryman, Agarwal, Lieberman, Fulgoni & Pasiakos, 2016; Pimpin, Jebb, Johnson, Wardle & Ambrosini, 2016). Nonetheless, the maintenance of body weight in older RedTg mice may be due to higher fat accumulation than in Wt controls, in agreement with our recent study that showed a positive correlation between mouse longevity and conservation of body fat (Mitchell et al., 2016).…”

Current Controversies around Carbohydrate Restriction and the Risk of High-Protein Diets

“…Solon-Biet et al 16 compared three regimens varying in protein to carbohydrate ratio under both Calorie Restriction (CR) and ad libitum conditions. These diets were classified as low-protein (5%), Low-protein high-carbohydrate (LPHC), medium-protein (33%), medium-carbohydrate and high-protein (60%), low-carbohydrate.…”