Guanidinoacetic Acid With Creatine Compared With Creatine Alone for Tissue Bioenergetics, Hyperhomocysteinemia and Exercise Performance

Guanidinoacetic Acid With Creatine Compared With Creatine Alone for Tissue Bioenergetics, Hyperhomocysteinemia and Exercise Performance: a Randomized Double-blind Superiority Trial

Co-administration of creatine and guanidinoacetic acid (GAA) has been recently put forward as an advanced dietary strategy to optimize tissue bioenergetics. The investigators hypothesized that creatine-GAA mixture would result in more powerful rise in brain and skeletal muscle creatine, as compared to creatine supplementation alone.

Study Overview

• Status: Completed
• Conditions: Energy Metabolism
• Intervention / Treatment: Dietary supplement: GAA-creatine; Dietary supplement: Creatine

Detailed Description

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. Creatine is recognized as a beneficial and safe energy-boosting agent in both athletic and clinical environments. However, its effectiveness in specific conditions seems to be fairly restrained due to its limits in transportability and performance. Guanidinoacetic acid (GAA), a metabolic precursor of creatine, appears as a novel energy-enhancing supplement, with GAA being superior to creatine in facilitating creatine concentrations in the human brain and skeletal muscle. This perhaps happens due to GAA interaction with cellular transporters previously dismissed as untargetable carriers by other similar therapeutics. On the other hand, GAA loading remains under scrutiny due to its hyperhomocysteinemia-inducing potential, and possible neurotoxic effects. Co-administration of creatine and GAA has been recently proposed as a better strategy comparing to administration of each compound per se. Besides providing a competitive advantage for enhanced levels of tissue creatine, GAA-creatine mixture might also diminish side effects related to isolated GAA administration. However, no human studies so far evaluated the effects of this mixture. In the present study, the investigators compared the impact of 4-week co-administration of GAA and creatine vs. creatine administration alone on serum biomarkers, exercise performance and tissue bioenergetics in healthy young men.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• men age 18-45 years
• BMI 18.5-24.9 kg/m2
• physically active (> 150 min per week)
• free of known disease
• must be able to give written informed consent

Exclusion Criteria:

• serum homocysteine > 15 µmol/L
• use of dietary supplement (> 1 month)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mixture GAA-creatine; Mixture of guanidinoacetic acid and creatine monohydrate	Dietary supplement: GAA-creatine
Active Comparator: Creatine; Creatine monohydrate	Dietary supplement: Creatine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain creatine	Rise in brain creatine levels	Baseline vs 4-week follow up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vastus medialis creatine	Rise in vastus medialis creatine creatine levels	Baseline vs 4-week follow up

Collaborators and Investigators

• Sponsor: University of Novi Sad, Faculty of Sport and Physical Education
• Investigators: Study Chair: Sergej Ostojic, MD, PhD, University of Novi Sad

Publications and helpful links

General Publications

• Ostojic SM. Co-administration of creatine and guanidinoacetic acid for augmented tissue bioenergetics: A novel approach? Biomed Pharmacother. 2017 Jul;91:238-240. doi: 10.1016/j.biopha.2017.04.075. Epub 2017 Apr 28.
• Semeredi S, Stajer V, Ostojic J, Vranes M, Ostojic SM. Guanidinoacetic acid with creatine compared with creatine alone for tissue creatine content, hyperhomocysteinemia, and exercise performance: A randomized, double-blind superiority trial. Nutrition. 2019 Jan;57:162-166. doi: 10.1016/j.nut.2018.04.009. Epub 2018 May 17.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2016
• Primary Completion (Actual): May 1, 2018
• Study Completion (Actual): May 1, 2018

Study Registration Dates

• First Submitted: November 17, 2017
• First Submitted That Met QC Criteria: November 17, 2017
• First Posted (Actual): November 22, 2017

Study Record Updates

• Last Update Posted (Actual): May 4, 2018
• Last Update Submitted That Met QC Criteria: May 3, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Nutrition Disorders; Genetic Diseases, Inborn; Avitaminosis; Deficiency Diseases; Malnutrition; Metabolism, Inborn Errors; Malabsorption Syndromes; Amino Acid Metabolism, Inborn Errors; Vitamin B Deficiency; Hyperhomocysteinemia
• Other Study ID Numbers: SSD-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: The data will be shared via institutional repository
• IPD Sharing Time Frame: Data will be available from January 2018
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No