Role of leucine on muscle preservation during weight loss in young and elderly men
Authors:   , Pang Benedict Wei Jun 
Published: February 2025

Overweightness and obesity are a burgeoning health epidemic. Many diets like alternate-day fasting (ADF) are effective in combatting obesity, but most studies are long in duration (8-48 weeks) which can be challenging and demotivating to people trying to lose weight. Importantly, the weight loss attained comes with significant muscle loss, which has dire health consequences especially among seniors who are at risk of developing sarcopenia. To combat muscle loss, dietary protein interventions have been examined. Protein stimulates muscle protein synthesis (MPS), a process that helps construct new muscle protein over time. However, there is evidence that increasing protein intake alone beyond normal recommended levels may not improve muscular outcomes. Leucine has been proposed to be the key driver of MPS and is even shown to reduce muscle protein breakdown. One important benefit of leucine over protein is the need to consume fewer overall nutrients and calories to attain the same MPS response: around 2-4 g of leucine maximises MPS compared to 20-40 g of protein. While absolute doses (e.g., 2-4 g) have been examined, a more useful and individualised leucine dose adjusted to body mass (e.g., g/kg) has not been determined. Additionally, the dose-response of different leucine amounts on muscular outcomes have not been investigated. In this doctoral thesis, a preliminary study was first conducted to ascertain short-term ADFâ€™s effects on weight loss and muscle loss. The results show that short-term ADF over just four weeks is effective in promoting weight and fat loss. However, it also led to significant muscle loss which was not attenuated by increased protein intake on the fasting day. Study 1 was then conducted to examine the efficacy of body mass-adjusted leucine doses on muscle preservation during weight loss, to determine if it is possible to lose weight without significant muscle loss through increased leucine intake. There were no significant interactions in changes/responses in body composition and muscular outcomes across groups, indicating that increased leucine intake was not efficacious, and a dose-response was not present, in preserving muscle. In Study 2, the effectiveness of body mass-adjusted leucine or protein supplementation, versus control, on muscular and sarcopenic outcomes during weight loss, was examined, to determine whether it is possible for seniors to lose weight without significant muscle loss through increased leucine and/or protein intake. There were no significant interactions in body composition, muscular or sarcopenic outcomes across groups, indicating that increased leucine or protein intake was not effective in preserving these outcomes. This thesis affirms ADF as a safe and effective weight loss strategy with high adherence rates among young and older men in Singapore. Increased leucine and/or protein intake is not effective in improving body composition and muscular outcomes during weight loss. While dietary leucine and protein have important roles to play, it is speculated that resistance exercise may be even more important to the muscle building/preservation equation. It is proposed that future studies implement a resistance exercise protocol when investigating the role of body mass-adjusted leucine doses on body composition and muscular outcomes.