Elsevier

Nutrition

Volume 57, January 2019, Pages 162-166
Nutrition

Applied nutritional investigation
Guanidinoacetic acid with creatine compared with creatine alone for tissue creatine content, hyperhomocysteinemia, and exercise performance: A randomized, double-blind superiority trial

https://doi.org/10.1016/j.nut.2018.04.009Get rights and content

Highlights

  • 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.

Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.

Trial registration

ClinicalTrials.gov NCT03350282.

Introduction

Targeting energy-demanding tissues in health and disease continues to be a challenging task in human nutrition and biomedicine. Impaired bioenergetics accompanies many different conditions, including cardiometabolic diseases, neurodegenerative disorders, or high-intensity exercise, with various dietary interventions developed to restore cellular energy [1], [2]. Creatine is recognized as a beneficial and safe energy-boosting agent in both athletic and clinical environments [3]. However, its effectiveness in specific conditions seems to be fairly restrained due to its limits in transportability and performance [4]. Guanidinoacetic acid (GAA), a metabolic precursor of creatine, appears is a novel energy-enhancing supplement, with GAA being superior to creatine in facilitating creatine concentrations in the human brain and skeletal muscle [5]. This perhaps is due to the interaction of GAA with cellular transporters previously dismissed as untargetable carriers by other similar therapeutics [6]. On the other hand, GAA loading remains under scrutiny due to its hyperhomocysteinemia-inducing potential [7] and possible neurotoxic effects [8]. Co-administration of creatine and GAA has been recently proposed as a better strategy than administration of each compound per se [9]. In addition to providing a competitive advantage for enhanced levels of tissue creatine, a GAA–creatine mixture also might diminish side effects related to isolated GAA administration. However, no human studies to date have evaluated the effects of this mixture. In the present study, the authors compared the effects of a 4-wk co-administration of GAA and creatine versus creatine administration alone on serum biomarkers, exercise performance, and tissue creatine content in healthy, active young men.

Section snippets

Participants

Fourteen healthy men (24.4 ± 4 y of age; weight 79.9 ± 13.9 kg; height 176.5 ± 7.3 cm) were recruited and signed informed consent to voluntarily participate in this double-blind, randomized, creatine-controlled, crossover trial examining the effects of a GAA–creatine mixture on tissue bioenergetics and exercise performance. Appropriate sample size (N = 12) was calculated using the power analysis (effect size 0.5, α error probability 0.05, power 0.80) for the primary outcome measure, an

Results

All participants completed the trial, with no subjective side effects reported during the intervention periods. Compliance was rather high and comparable in both groups (91.8% ± 17.2% for the GAA–creatine group, 88.8% ± 20.1% for the creatine-alone group), as evaluated by counting unconsumed sachets at follow-up. Changes in physical, biochemical, and physiological indices during the study are depicted in Table 1. Compared with creatine administration alone, the GAA–creatine mix resulted in less

Discussion

In the present study, the authors confirmed the prespecified hypothesis that the GAA–creatine mixture results in more powerful elevation of tissue creatine than equimolar creatine. Furthermore, better outcomes also were reported for upper body muscular strength and less weight gain in the GAA–creatine group, with no side effects and clinically relevant disturbances in tHcy and serum creatinine. This perhaps advances the GAA–creatine mixture as an effective and safe creatine-boosting and

Conclusion

A 1-to-3 GAA–creatine mixture was found to be superior to pure creatine for improved brain and muscle creatine levels, and upper body muscular strength, accompanied by less weight gain after a 4-wk intervention in healthy, physically active men. This mixture, referring to dosage used in this study, has been found harmless concerning the risk for hyperhomocysteinemia or brain choline depletion. Nevertheless, more randomized controlled trials are needed before the GAA–creatine mixture can be

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Cited by (0)

This study was supported by the Serbian Ministry of Education, Science and Technological Development (175037), the Provincial Secretariat for Higher Education and Scientific Research (114-451-710), the Faculty of Sport and Physical Education, and the Center for Health, Exercise and Sport Sciences. The funders had no role in study design, data collection, analysis, and interpretation, decision to publish, or preparation of the manuscript. SMO contributed to the conception of the study and drafted the manuscript. SS, VS, JO, and MV contributed to the acquisition and analysis of the data. SS and SMO contributed to the interpretation of the data. All authors contributed to the design of the research, critically revised the manuscript, and read and approved the final manuscript. The authors have no conflicts of interest to report.

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