Explore the vast range of titles available.

•Guanidinoacetic acid (GAA) appears to be a novel energy-enhancing supplement for brain and muscle.•The combination of creatine and GAA results in more powerful elevation of tissue creatine than equimolar creatine.•Better outcomes were reported for upper body muscular strength and less weight gain in the GAA–creatine group.•The GAA–creatine mixture is an effective and safe creatine-boosting alternative to creatine alone in healthy men. Co-administration of creatine and guanidinoacetic acid (GAA) has been recently put forward as an advanced dietary strategy to optimize tissue bioenergetics. We hypothesized that creatine-GAA mixture would result in a more powerful rise in brain and skeletal muscle creatine, as compared to creatine supplementation alone. A randomized, double-blinded, crossover superiority trial has been performed at the University of Novi Sad from December 2016 to November 2017. A total of 14 healthy young men were randomized to receive GAA-creatine mixture (1 grams of GAA and 3 grams of creatine per day) or equimolar creatine (4 grams per day) by oral administration for 4 weeks. Creatine-GAA mixture was superior to creatine alone to increase mean creatine levels in skeletal muscle (16.9 ± 20.2 vs. 2.0 ± 6.0%; P = 0.02) and grey matter (5.8 ± 5.3% vs. 1.5 ± 3.2%; P = 0.02), also for bench press performance (6.0% vs. 5.1%; P < 0.01). Compared with creatine administration alone, combined GAA and creatine resulted in less weight gain (1.6 ± 0.2 kg vs. 0.7 ± 0.2 kg; P < 0.01). No inter-group differences were observed in terms of cardiorespiratory endurance, serum biomarkers, or adverse events. Creatine-GAA mixture appeared to be superior to creatine alone for up-swinging tissue creatine content and upper body strength, and tended toward a lower risk of weight gain in healthy active men. The formulation might be considered as a novel energy-boosting alternative to creatine alone in weight-sensitive setups. ClinicalTrials.govNCT03350282.