Guanidinoacetic Acid (GAA) Administration in Physically Active Men and Women

December 18, 2011 updated by: Sergej M. OSTOJIC, Metropolitan University, Serbia

The Effects of Medium-term Oral Guanidinoacetic Acid (GAA) Administration on Human Performance, Body Composition, and Metabolic Outcomes in Physically Active Men and Women

Glycocyamine (guanidinoacetic acid - GAA) is the biochemical precursor of creatine, which is phosphorylated and plays an important role as a high-energy carrier in the muscle. Since GAA can be administered in liquid solutions, such as sports drinks, it could be hypothesised that GAA could easily enhance creatine biosynthesis with clear physiological effects yet to be determined. No single study has examined the influence of GAA on health, human performance or body composition indicators in healthy human subjects. Moreover, the most effective dose of GAA is yet to be find. Finally, the adverse effects of GAA supplementation in humans are not determined. The main aims of the present study will be to identify if the 6-weeks of GAA supplementation improves human performance and body composition, to determine most effective dose regimens of GAA, and to analyze adverse effects of GAA supplementation. Forty eight healthy, trained (> 2 yr training experience) male and female subjects (aged 20 to 25 years) will give their informed consent and volunteer to participate in the study, which will obtain the approval of the University's Ethical Advisory Commission. The subjects will be allocated to four randomly assigned trials: ingesting GAA (1.2, 2.4, 4.8 g of GAA in a single dose) or placebo (PLA) for 6 weeks in a double-blind design. All testing including blood and urine samples, body composition and muscle strength and exercise performance (both aerobic and anaerobic) will be conducted at presupplementation (baseline), at 1 week, at 2 weeks, at 4 weeks, at 6 weeks of supplementation and at 8 and 10 weeks (2 and 4 weeks after the end of supplementation) to analyze wash-out period. According to previous investigations, the investigators expect that ingestion of GAA will significantly increase both serum creatine and total homocystein. The investigators expect that ingestion of GAA will significantly improve muscle strength parameters and exercise performance results as compared to placebo in long term. The investigators also expect to find prevalence of side-effects (i.e. gastrointestinal distress, retention of fluid).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

For the last two decades, top athletes first, then sport professionals and amateur sports participants have been using oral creatine supplementation on regular basis as an ergogenic aid to improve performance (Poortmans & Francaux 2000). Up to 90% of team-game athletes are regular consumers of creatine (Striegel et al. 2006), with nearly 60% of recreational athletes have tried creatine (Froiland et al. 2004). Supplementation with oral creatine, that currently is viewed to be safe, augments skeletal muscle creatine concentrations in most individuals, which has been shown to promote gains in lean body mass when used in conjunction with resistance training, to enhance power and strength, and to improve performance in intense exercise, especially during repeated bouts (Racette 2003; Ostojic 2004). Yet, creatine is not stable in solution and as such is only offered in a variety of non-liquid forms including powder, tablets, gel, chewing gum, and candy (Benzi & Ceci 2001). Although creatine synthesis is a proprietary process among manufacturers, it is quite common to use another muscle-related compounds (i.e. sarcosine, cyanamide), as the principal starting materials for the commercial synthesis of creatine (Williams & Branch 1998). Glycocyamine (guanidinoacetic acid - GAA) along with L-ornithine is formed from arginine and glycine in the kidney, with this reaction is believed to be the regulated step of creatine biosynthesis (Edison et al. 2007). The second enzyme in the pathway is GAA N-methyltransferaze which catalyzes the transfer of a methyl group from S-adenosylmethionine (SAM) to GAA to form S-adenosylhomocysteine (SAH) and creatine (Walker 1979). It has been estimated that about 75% of labile methyl groups is used to synthetize creatine by a reaction catalyzed by GAA N-methyltransferaze (Mudd et al. 1975). It seems that creatine synthesis is an interorgan process whereby GAA, produced by the kindey, is released into the circulation and is methylated to creatine in the liver. Creatine is then released from the liver and into the circulation where it can be taken up, via a specific transporter, by various tissues. According to previous studies in animals (da Silva et al. 2009) and preliminary research in humans (AlzChem 2009), short-term oral intake of GAA increases serum level of creatine, with level of increase interrelated with GAA dose supplemented. GAA is the biochemical presursor of creatine, which is phosphorylated and plays an important role as a high-energy carrier in the muscle (Edison et al. 2007). Since GAA can be administred in liquid solutions, such as sports drinks, it could be hypothesised that GAA could easily enhance creatine biosynthesis with clear physiological effects yet to be determined. Moreover, it seems that GAA has a significantly better bioavailability than creatine, developing maximal activity at a dosage at which creatine leads to no observable effects (AlzChem 2009). Several human studies (Borsook & Borsook 1951; Graybiel & Patterson 1951; Higgins et al. 1952; Dixon et al. 1954) found beneficial effects of creatine precursors oral administration on cardiac decompensation, arthritis, anxiety and depression patients. Authors speculated that benefical effects of GAA intake could be due to boosting energy levels and/or increased availability of dimethylglycine for incorporation into tissue proteins, providing repair of damaged muscle cells. Yet, no single study has examined the influence of additive-free GAA (e.g. without betaine or choline) on health, human performance or body composition indices. The amount taken of this supplementation ranges typically from a few grams to tens of grams per day for weeks or months in previous research in humans. Although, the most effective dose is yet to be find. Finally, the adverse effects of GAA supplementation in both animals and humans are yet to be determined. Several studies showed moderate hyperhomocysteinemia (Stead et al. 2001; Fukada et al. 2006; Setoue et al. 2008; AlzChem 2009), disturbances in antioxidant system (Zugno et al. 2008), modulation of inflammatory responses (Glorieux et al. 2004) after GAA supplementation. If GAA have ergogenic properties it could become new effective performance-enhancing substance for both professional and recreational athletes, stable in water solutions, where creatine at neutral to slightly acidic pH-values is rapidly being metabolised to creatinine, which is meaningless for the energy production (AlzChem 2009).

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Serbia
    • Vojvodina
      • Novi Sad, Vojvodina, Serbia, 21000
        • Biomedical Scinces Department, Exercise Physiology Lab

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 25 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • healthy young men and women
  • aged 20 to 25 years
  • experienced in athletic training
  • free from musculoskeletal dysfunctions
  • free from metabolic and heart diseases
  • participating in consistent training (average of three times per week)

Exclusion Criteria:

  • current intake of dietary supplement containing performance-enhancing agent
  • pregnant women
  • current intake of hormonal contraceptives

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: GAA-2
2.4 grams of guanidinoacetic acid
Dietary supplement: guanidinoacetic acid
2.4 grams of guanidinoacetic acid
Experimental: GAA-1
1.2 grams of guanidinoacetic acid
Dietary supplement: GAA-1
1.2 grams of guanidinoacetic acid
Experimental: GAA-4
4.8 grams of guanidinoacetic acid
Dietary supplement: GAA-4
4.8 grams of guanidinoacetic acid
Placebo Comparator: PLACEBO
cellulose
Dietary supplement: PLACEBO
celulose

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Muscle power
Time Frame: Baseline, at 1 week, at 2 weeks, at 4 weeks, at 6 weeks, at 8 weeks, at 10 weeks
The majority of investigations involving the effects of creatine (or creatine precursors) supplementation on human performance were laboratory-based and have focused on musucular strength and power and anaerobic endurance, with various task protocols such as weght lifting, running, jumping and cycling less than or equal to 30 sec in duration. Similarly, the effects of GAA on exercise performance should be investigated with measuring muscle strength and power (through both isometric and isotonic exercise) and anaerobic endurance (e.g. repeated jumping performance).
Baseline, at 1 week, at 2 weeks, at 4 weeks, at 6 weeks, at 8 weeks, at 10 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Muscle mass
Time Frame: Baseline, at 1 week, at 2 weeks, at 4 weeks, at 6 weeks, at 8 weeks and at 10 weeks
A creatine supplementation-induced increase in body mass, particularly if not muscle mass, could be detrimental to performance in sports in which the body mass needs to be moved efficiently from one point to another. If GAA acts as creatine, which is an osmotically active substance, an increase in intracellular creatine concentration may likely induce influx of water into the cell. Therefore, changes of body mass and body composition (particularly muscle mass) after GAA intake should be monitored during the present study.
Baseline, at 1 week, at 2 weeks, at 4 weeks, at 6 weeks, at 8 weeks and at 10 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Metropolitan University, Serbia

Investigators

  • Principal Investigator: Sergej M Ostojic, MD, PhD, Biomedical Sciences Dept, Faculty of Sport Sciences and Tourism, Metropolitan University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2010

Primary Completion (Actual)

December 1, 2011

Study Completion (Actual)

December 1, 2011

Study Registration Dates

First Submitted

May 28, 2010

First Submitted That Met QC Criteria

May 28, 2010

First Posted (Estimate)

May 31, 2010

Study Record Updates

Last Update Posted (Estimate)

December 20, 2011

Last Update Submitted That Met QC Criteria

December 18, 2011

Last Verified

December 1, 2011

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • AN-85E-S09

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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