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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Energy Metabolism

Intervention / Treatment
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* Dietary Supplement: GAA-creatine
* Dietary Supplement: Creatine


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mixture GAA-creatine<br>Mixture of guanidinoacetic acid and creatine monohydrate | Dietary Supplement: GAA-creatine<br> <br> |
| Active Comparator: Creatine<br>Creatine monohydrate | Dietary Supplement: Creatine<br> <br> |

What is the study measuring?
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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 |