Obesity and Metabolic Disease Impair the Anabolic Response to Protein Supplementation and Resistance Exercise: A Retrospective Analysis of a Randomized Clinical Trial with Implications for Aging, Sarcopenic Obesity, and Weight Management.

BACKGROUND

Anabolic resistance accelerates muscle loss in aging and obesity, thus predisposing to sarcopenic obesity.

METHODS

In this retrospective analysis of a randomized clinical trial, we examined baseline predictors of the adaptive response to three months of home-based resistance exercise, daily physical activity, and protein-based, multi-ingredient supplementation (MIS) in a cohort of free-living, older males ( = 32).

RESULTS

Multiple linear regression analyses revealed that obesity and a Global Risk Index for metabolic syndrome (MetS) were the strongest predictors of Δ% gains in lean mass (TLM and ASM), LM/body fat ratios (TLM/%BF, ASM/FM, and ASM/%BF), and allometric LM (ASMI, TLM/BW, TLM/BMI, ASM/BW), with moderately strong, negative correlations to the adaptive response to polytherapy r = -0.36 to -0.68 ( < 0.05). Kidney function, PA level, and chronological age were only weakly associated with treatment outcomes ( > 0.05). Next, we performed a subgroup analysis in overweight/obese participants with at least one other MetS risk factor and examined their adaptive response to polytherapy with two types of protein-based MIS (PLA; collagen peptides and safflower oil, = 8, M5; whey/casein, creatine, calcium, vitamin D, and fish oil, = 12). The M5 group showed greater improvements in LM (ASM; +2% vs. -0.8%), LM/body fat ratios (ASM/FM; +3.8% vs. -5.1%), allometric LM (ASM/BMI; +1.2% vs. -2.5%), strength (leg press; +17% vs. -1.4%), and performance (4-Step-Stair-Climb time; -10.5% vs. +1.1%) vs. the PLA group ( < 0.05). Bone turnover markers, indicative of bone accretion, were increased pre-to-post intervention in the M5 group only (P1NP; = 0.036, P1NP/CTX ratio; = 0.088). The overall anabolic response, as indicated by ranking low-to-high responders for Δ% LM ( = 0.0079), strength ( = 0.097), and performance ( = 0.19), was therefore significantly higher in the M5 vs. PLA group ( = 0.013).

CONCLUSIONS

Our findings confirm that obesity/MetS is a key driver of anabolic resistance in old age and that a high-quality, whey/casein-based MIS is more effective than a collagen-based alternative for maintaining musculoskeletal health in individuals at risk for sarcopenic obesity, even when total daily protein intake exceeds current treatment guidelines.