Comparative Effects of Guanidinoacetic Acid and Creatine on Body Composition, Muscle Strength, and Protein Metabolism Biomarkers in Older Adults: A Randomized Exploratory Pilot Trial

Creatine supplementation can improve muscle outcomes in older adults, particularly when combined with resistance exercise; however, its efficacy without exercise is less consistent. Guanidinoacetic acid (GAA), the immediate precursor of creatine, may bypass age-related limitations in creatine synthesis and transport and exert distinct effects on muscle energetics and protein metabolism. The main aim of the study was compare the effects of 8 wk of GAA versus creatine supplementation on muscle strength, body composition, and selected protein metabolism biomarkers in older adults. In this randomized, double-blind, exploratory pilot trial, 25 apparently healthy adults aged ≥65 y were assigned to receive GAA (2.0 g/d) or an equimolar dose of creatine monohydrate for 8 wk. Twenty-one participants completed the study (GAA, n=11; creatine, n=10). Handgrip strength, body composition and fluid compartments (via multifrequency bioelectrical impedance analysis), and circulating myostatin, insulin-like growth factor-1, mammalian target of rapamycin, total homocysteine, albumin, and total protein were assessed at baseline and follow-up. Intervention effects were evaluated using repeated-measures ANOVA, and between-group effect sizes for change scores were estimated using Hedges' g with 95% confidence intervals. Handgrip strength increased significantly with GAA (p=0.01) but not with creatine, with a significant time-by-treatment interaction (p=0.04) and a large between-group effect favoring GAA (g=0.91, 95% CI: 0.00 to 1.81). GAA supplementation was associated with significant within-group increases in fat-free mass, body cell mass, muscle mass, and total body water, whereas creatine supplementation did not produce comparable changes. Effect size analyses generally favored GAA for strength, muscle-related indices, and hydration-related compartments, although confidence intervals were wide. Both supplements reduced circulating myostatin, with greater suppression observed with GAA. Creatine supplementation produced a modest reduction in serum albumin that remained within physiological reference ranges. Serum IGF-1 concentrations were below the assay detection limit in most participants, precluding evaluation of the GH-IGF-1 axis. No adverse events were reported, and compliance exceeded 97% in both groups. In this exploratory pilot trial conducted without structured exercise, GAA supplementation was associated with numerically greater improvements in muscle strength and several muscle-related indices compared with creatine; however, these findings are preliminary and hypothesis-generating and require confirmation in adequately powered trials targeting sarcopenia.