Guanidinoacetic Acid

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Sergej M. Ostojic - One of the best experts on this subject based on the ideXlab platform.

  • molecular docking and density functional theory studies on creatine Guanidinoacetic Acid and their phosphorylated analogues binding to muscle creatine kinase
    Journal of Chemical Research-s, 2021
    Co-Authors: Milan Vraneš, Sergej M. Ostojic, Crtomir Podlipnik, Aleksandar Tot
    Abstract:

    Comparative molecular docking studies on creatine and Guanidinoacetic Acid, as well as their phosphorylated analogues, creatine phosphate, and phosphorylated Guanidinoacetic Acid, are investigated....

  • Guanidinoacetic Acid loading for improved location specific brain creatine
    Clinical Nutrition, 2021
    Co-Authors: Sergej M. Ostojic
    Abstract:

    Summary Background We conducted here a secondary analysis of previously completed Guanidinoacetic Acid (GAA) loading trials categorizing participants into responders and non-responders using cut-off points for an increase in the location-specific levels of brain creatine (e.g. thalamus, cerebellum, white and grey matter). Methods A total of 19 healthy men (mean age = 24.8 years) who were supplemented with 3 g/d of GAA for 4 weeks, with total brain creatine evaluated using 1.5 T magnetic resonance spectroscopy (MRS) were included in this report. Results An average elevation in total creatine content after 28-day GAA loading was 17.3% in the cerebellum (95% confidence interval [CI] from 9.7 to 24.9), 12.1% in the white matter (95% CI from 5.1 to 19.1), and 8.9% in the grey matter (95% CI from 5.2 to 12.6), while total creatine actually dropped in the thalamus at a follow-up for 9.1% (95% CI from 6.8 to 11.4). The prevalence of responders was the highest for the cerebellum (73.6%), followed by the white matter (47.3%) and the grey matter (42.1%), while only two individuals (10.5%) experienced a relevant rise in the thalamus creatine content at 28-day follow-up (P  Conclusion This aftermath evaluation of previously published data suggests a relatively favorable (and location-specific) response rate to short-term GAA loading in healthy young men. A somewhat contrasting location-dependent pattern for GAA and creatine to positively affect brain creatine may be of great interest to the scientific community by dispensing different interventions to tackle poor bioenergetics in distinct brain regions.

  • Guanidinoacetic Acid as a novel food for skeletal muscle health
    Journal of Functional Foods, 2020
    Co-Authors: Sergej M. Ostojic, Viktoria Premusz, Dora Nagy, Pongrac Acs
    Abstract:

    Abstract Guanidinoacetic Acid (GAA) is a direct endogenic precursor of creatine. GAA is also a re-discovered nutraceutical that has been put forward as an energy-facilitating compound by many animal and a few human studies. Recent trials indicated that dietary GAA might have yet another role in muscle growth promotion, acting as an anticatabolic and/or anabolic compound. This opinion paper summarizes the latest findings for advancing (or impeding) dietary GAA in skeletal muscle medicine, discussing open questions that need to be answered before the translation of supplemental GAA use from bench to bedside.

  • Guanidinoacetic Acid deficiency: a new entity in clinical medicine?
    International journal of medical sciences, 2020
    Co-Authors: Sergej M. Ostojic, Laszlo Ratgeber, András Oláh, József Betlehem, Pongras Acs
    Abstract:

    Guanidinoacetic Acid (GAA, also known as glycocyamine or betacyamine) is a naturally-occurring derivative of glycine and a direct metabolic precursor of creatine, a key player in high-phosphate cellular bioenergetics. GAA is found in human serum and urine, with circulating GAA likely reflects an equilibrium between its endogenous production and utilization/excretion. GAA deficiency (as indicated by low serum GAA) has been reported in various conditions yet this intriguing clinical entity appears to be poorly characterized as yet, either as a primary deficit or a sequel of secondary disease. This minireview article summarizes the inherited and acquired disorders with apparent GAA deficiency and discusses a possible relevance of GAA shortfall in clinical medicine.

  • human gut microbiota as a source of Guanidinoacetic Acid
    Medical Hypotheses, 2020
    Co-Authors: Sergej M. Ostojic
    Abstract:

    Guanidinoacetic Acid (GAA) is a natural amino Acid derivative that acts as a precursor of creatine while being synthesized and utilized in a two-step reaction that takes place in the human kidney and liver. In this paper, we have proposed that guanidinoacetase, an enzyme present in healthy gut microbiota, might contribute to gross GAA turnover by hydrolyzing GAA to glycine and urea or vice versa. Additional studies are thus needed to assess a net gain of this microbiota-driven GAA pathway that may account for energy metabolism homeostasis in general.

Milan Vraneš - One of the best experts on this subject based on the ideXlab platform.

  • molecular docking and density functional theory studies on creatine Guanidinoacetic Acid and their phosphorylated analogues binding to muscle creatine kinase
    Journal of Chemical Research-s, 2021
    Co-Authors: Milan Vraneš, Sergej M. Ostojic, Crtomir Podlipnik, Aleksandar Tot
    Abstract:

    Comparative molecular docking studies on creatine and Guanidinoacetic Acid, as well as their phosphorylated analogues, creatine phosphate, and phosphorylated Guanidinoacetic Acid, are investigated....

  • Guanidinoacetic Acid with creatine compared with creatine alone for tissue creatine content, hyperhomocysteinemia, and exercise performance: A randomized, double-blind superiority trial.
    Nutrition, 2018
    Co-Authors: Sasa Semeredi, Milan Vraneš, Jelena Ostojic, Valdemar Stajer, Sergej M. Ostojic
    Abstract:

    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  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 .

  • Guanidinoacetic Acid and creatine are associated with cardiometabolic risk factors in healthy men and women a cross sectional study
    Nutrients, 2018
    Co-Authors: Sergej M. Ostojic, Milan Vraneš, Natasa Zenic, Davor Loncar, Damir Sekulic
    Abstract:

    Guanidinoacetic Acid (GAA) conversion to creatine is thought to be involved in cardiometabolic disturbances through its role in biological methylation and insulin secretion. We evaluated the association of serum GAA and creatine with cardiometabolic risk factors in a cohort of 151 apparently healthy adults (82 women and 69 men) aged 18-63 years. Serum levels of GAA and creatine were measured with liquid chromatography-tandem mass spectrometry. A multiple linear regression model adjusted for age and sex was employed to examine the relationship of serum GAA and creatine with cardiometabolic risk factors. Higher GAA levels were associated with an unfavorable cardiometabolic risk profile (higher insulin, higher total homocysteine, and higher body fat percentage), while having elevated serum creatine levels (≥31.1 µmol/L) was associated with being overweight (body mass index ≥ 25.0 kg/m). The results from our study suggest a possible role of the GAA-creatine axis in the pathogenesis of cardiovascular and metabolic diseases.

  • does dietary provision of Guanidinoacetic Acid induce global dna hypomethylation in healthy men and women
    Lifestyle genomics, 2018
    Co-Authors: Sergej M. Ostojic, Patrik Drid, Marija Mojsin, Milan Vraneš
    Abstract:

    Background/aims Guanidinoacetic Acid (GAA) is an experimental dietary additive and has been reported to induce methyl depletion when provided by the diet. However, no study evaluated whether supplemental GAA affects DNA methylation, a critical epigenetic process for genome regulation. Methods In this open-label, repeated-measure interventional trial, we evaluated the impact of 12 weeks of GAA supplementation on global DNA methylation in 14 healthy participants (8 women and 6 men, age 22.2 ± 2.3 years, body mass index 24.8 ± 5.7). Results Dietary provision of GAA had no effect on global DNA methylation, with 5-methylcytosine (m5C) nonsignificantly increased by 13.4% at postadministration when averaged across participants (95% confidence interval -5.5 to 32.3; p = 0.26). Notable DNA hypomethylation (corresponding to a 5% drop in m5C) was found in 3 of 14 participants at follow-up. Conclusion Global DNA methylation seems to be unaltered by dietary provision of 3 g of GAA per day for 12 weeks in healthy men and women.

  • experimental and computational study of Guanidinoacetic Acid self aggregation in aqueous solution
    Food Chemistry, 2017
    Co-Authors: Milan Vraneš, Sergej M. Ostojic, Aleksandar Tot, Snežana Papovic, Slobodan Gadžuric
    Abstract:

    Abstract In this work for the first time the physicochemical and thermal properties of Guanidinoacetic Acid (GAA) and its aqueous solutions have been performed to test for its viability as a potential dietary supplement. Thermal stability, viscosity, solubility and experimental density are determined. From measured densities the volumetric properties were estimated and discussed in the scope of GAA self-aggregation in aqueous solutions using experimental and computational results. Based on thermal stability and solubility measurements, it is found that GAA is more thermally stable but less soluble comparing to creatine due to a self-aggregation process that occurs at GAA concentrations higher than 0.013 mol · dm−3. Existence of self-aggregation influences the macroscopic properties of aqueous GAA solutions, but also its bioavailability.

Jelena Ostojic - One of the best experts on this subject based on the ideXlab platform.

  • Dietary Guanidinoacetic Acid does not accumulate in the brain of healthy men
    European Journal of Nutrition, 2018
    Co-Authors: Sergej M. Ostojic, Jelena Ostojic
    Abstract:

    We conducted a secondary analysis of a previously completed trial to determine the effects of 8-week Guanidinoacetic Acid (GAA) loading on brain GAA levels in five healthy men. Brain magnetic resonance spectroscopy (1H-MRS) was taken at baseline and post-administration, with spectra additionally analyzed for brain GAA and glutamate concentrations using TARQUIN 4.3.10 software. Brain GAA levels remained essentially unchanged at follow-up (an increase of 7.7% from baseline levels; 95% confidence interval, - 24.1% to 39.5%; P = 0.88) when averaged across 12 white and grey matter voxel locations. No significant changes were found for brain glutamate levels during the study (P = 0.64). Supplemental GAA appears to be safe intervention concerning brain GAA deposition, at least with GAA dosages used.

  • Guanidinoacetic Acid with creatine compared with creatine alone for tissue creatine content, hyperhomocysteinemia, and exercise performance: A randomized, double-blind superiority trial.
    Nutrition, 2018
    Co-Authors: Sasa Semeredi, Milan Vraneš, Jelena Ostojic, Valdemar Stajer, Sergej M. Ostojic
    Abstract:

    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  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 .

  • human skeletal muscle contains no detectable Guanidinoacetic Acid
    Applied Physiology Nutrition and Metabolism, 2018
    Co-Authors: Sergej M. Ostojic, Jelena Ostojic
    Abstract:

    We analyzed data from previously completed trials to determine the effects of supplemental Guanidinoacetic Acid (GAA) on markers of muscle bioenergetics in healthy men using 1.5 T magnetic resonance spectroscopy. No detectable GAA (<0.1 μmol/L) was found in the vastus medialis muscle at baseline nor at follow-up. This implies deficient GAA availability in the human skeletal muscle, suggesting absent or negligible potential for creatine synthesis from GAA inside this tissue, even after GAA loading.

  • dietary Guanidinoacetic Acid increases brain creatine levels in healthy men
    Nutrition, 2017
    Co-Authors: Sergej M. Ostojic, Jelena Ostojic, Patrik Drid, Milan Vraneš, Pavle Jovanov
    Abstract:

    Objective Guanidinoacetic Acid (GAA) is an experimental dietary additive that might act as a creatine source in tissues with high-energy requirements. In this case study, we evaluated brain levels of creatine in white matter, gray matter, cerebellum, and thalamus during 8 wk oral GAA administration in five healthy men and monitored the prevalence and severity of side effects of the intervention. Methods Volunteers were supplemented daily with 36 mg/kg body weight (BW) of GAA for the first 4 wk of the intervention; afterward GAA dosage was titrated ≤60 mg/kg BW of GAA daily. At baseline, 4, and 8 wk, the participants underwent brain magnetic resonance spectroscopy, clinical chemistry studies, and open-ended questionnaire for side-effect prevalence and severity. Results Brain creatine levels increased in similar fashion in cerebellum, and white and gray matter after GAA supplementation, with an initial increase of 10.7% reported after 4 wk, and additional upsurge (7.7%) from the weeks 4 to 8 follow-up (P < 0.05). Thalamus creatine levels decreased after 4 wk for 6.5% (P = 0.02), and increased nonsignificantly after 8 wk for 8% (P = 0.09). GAA induced an increase in N-acetylaspartate levels at 8-wk follow-up in all brain areas evaluated (P < 0.05). No participants reported any neurologic adverse event (e.g., seizures, tingling, convulsions) during the intervention. Conclusions Supplemental GAA led to a region-dependent increase of the creatine pool in the human brain. This might be relevant for restoring cellular bioenergetics in disorders characterized by low brain creatine and functional enzymatic machinery for creatine synthesis, including neurodegenerative diseases, brain tumors, or cerebrovascular disease.

  • Guanidinoacetic Acid versus creatine for improved brain and muscle creatine levels: a superiority pilot trial in healthy men
    Applied physiology nutrition and metabolism = Physiologie appliquee nutrition et metabolisme, 2016
    Co-Authors: Sergej M. Ostojic, Jelena Ostojic, Patrik Drid, Milan Vraneš
    Abstract:

    In this randomized, double-blind, crossover trial, we evaluated whether 4-week supplementation with Guanidinoacetic Acid (GAA) is superior to creatine in facilitating creatine levels in healthy men (n = 5). GAA (3.0 g/day) resulted in a more powerful rise (up to 16.2%) in tissue creatine levels in vastus medialis muscle, middle-cerebellar peduncle, and paracentral grey matter, as compared with creatine (P < 0.05). These results indicate that GAA as a preferred alternative to creatine for improved bioenergetics in energy-demanding tissues.

Marko Stojanovic - One of the best experts on this subject based on the ideXlab platform.

  • supplementation with Guanidinoacetic Acid in women with chronic fatigue syndrome
    Nutrients, 2016
    Co-Authors: Sergej M. Ostojic, Patrik Drid, Marko Stojanovic, Jay R Hoffman, Damir Sekulic, Natasa Zenic
    Abstract:

    A variety of dietary interventions has been used in the management of chronic fatigue syndrome (CFS), yet no therapeutic modality has demonstrated conclusive positive results in terms of effectiveness. The main aim of this study was to evaluate the effects of orally administered Guanidinoacetic Acid (GAA) on multidimensional fatigue inventory (MFI), musculoskeletal soreness, health-related quality of life, exercise performance, screening laboratory studies, and the occurrence of adverse events in women with CFS. Twenty-one women (age 39.3 ± 8.8 years, weight 62.8 ± 8.5 kg, height 169.5 ± 5.8 cm) who fulfilled the 1994 Centers for Disease Control and Prevention criteria for CFS were randomized in a double-blind, cross-over design, from 1 September 2014 through 31 May 2015, to receive either GAA (2.4 grams per day) or placebo (cellulose) by oral administration for three months, with a two-month wash-out period. No effects of intervention were found for the primary efficacy outcome (MFI score for general fatigue), and musculoskeletal pain at rest and during activity. After three months of intervention, participants receiving GAA significantly increased muscular creatine levels compared with the placebo group (36.3% vs. 2.4%; p < 0.01). Furthermore, changes from baseline in muscular strength and aerobic power were significantly greater in the GAA group compared with placebo (p < 0.05). Results from this study indicated that supplemental GAA can positively affect creatine metabolism and work capacity in women with CFS, yet GAA had no effect on main clinical outcomes, such as general fatigue and musculoskeletal soreness.

  • six week oral Guanidinoacetic Acid administration improves muscular performance in healthy volunteers
    Journal of Investigative Medicine, 2015
    Co-Authors: Sergej M. Ostojic, Marko Stojanovic, Jay R Hoffman
    Abstract:

    Background Guanidinoacetic Acid (GAA), a natural precursor of creatine, is a new promising dietary supplement, yet its performance-enhancing effect, if any, has yet to be established. The purpose of this pilot study was to evaluate the effects of supplemental GAA on muscle strength, anaerobic performance, and aerobic performance in healthy men and women. Method The study enrolled 48 young participants (age, 22.3 ± 1.5 years; height, 176.4 ± 10.0 cm; weight, 71.9 ± 14.3 kg), who received oral doses of GAA (1.2, 2.4, or 4.8 g/d) for 6 weeks in a randomized, double-blind, placebo-controlled trials. Results Significant differences were observed between treatment groups for handgrip strength among participants receiving 1.2 g of GAA per day and 2.4 g of GAA per day, as compared with placebo (P Conclusions Results from this preliminary study indicate that supplemental GAA ingested in young individuals can improve exercise performance, even at low doses (1.2 g/d).

  • Guanidinoacetic Acid loading affects plasma γ aminobutyric Acid in healthy men
    European Journal of Nutrition, 2015
    Co-Authors: Sergej M. Ostojic, Marko Stojanovic
    Abstract:

    Purpose Guanidinoacetic Acid (GAA), a precursor of creatine and an innovative dietary agent, activates γ-amino butyric Acid (GABA) receptors yet clinical effects of dietary GAA on GABA metabolism are currently unknown. The main aim of this pilot research was to investigate whether GAA loading affected peripheral GABA homeostasis in healthy humans.

  • dose response effects of oral Guanidinoacetic Acid on serum creatine homocysteine and b vitamins levels
    European Journal of Nutrition, 2014
    Co-Authors: Sergej M. Ostojic, Patrik Drid, Marko Stojanovic, Jay R Hoffman
    Abstract:

    Purpose Guanidinoacetic Acid (GAA) is an intermediate in the biosynthesis of creatine (Cr), yet its use in human nutrition is limited due to a lack of a clear understanding of its’ dose–response effect. Thus, the purpose of this study was to investigate the effect of three different dosages of GAA (1.2, 2.4 and 4.8 g/day) administered for 6 weeks on serum and urinary variables related to GAA metabolism.

  • serum creatine creatinine and total homocysteine concentration time profiles after a single oral dose of Guanidinoacetic Acid in humans
    Journal of Functional Foods, 2014
    Co-Authors: Sergej M. Ostojic, Marko Stojanovic, Barbara Niess, Kemal Idrizovic
    Abstract:

    Abstract Guanidinoacetic Acid (GAA) is a suitable feed additive yet its possible application in human nutrition as a food supplement requires preliminary pharmacokinetics data. The aim of the present study was to explore the effects of an acute oral dose of GAA on serum GAA, creatine (Cr), creatinine (Crn), and total homocysteine (T-Hcy) concentration-time profiles and urinary excretion rates of GAA, Cr and Crn. Twenty-four young healthy participants (age 22.3 ± 1.3 years; 12 males and 12 females) voluntarily ingested a single dose of GAA (2.4 g) or placebo (inulin) followed by the serial measurement of serum GAA, Cr, Crn and T-Hcy and urinary GAA, Cr and Crn concentration within the next 24 h. In response to GAA ingestion a substantial rise in serum GAA and Cr concentration was observed occurring 1 h after the ingestion (peak value of 144.9 ± 24.8 μmol/L and 65.5 ± 18.6 μmol/L, respectively). The Crn serum profile for 24 h was not affected by 2.4 g GAA ingestion, showing a peak value of 90.1 ± 12.2 μmol/L 1 h post-administration. A single dose of GAA induced a notable rise in serum T-Hcy by about 40%. The peak value was observed 12 h post administration (13.1 ± 2.1 μmol/L). Urinary excretion for GAA and Cr peaked after 4 h (453.1 ± 235.0 mg/L and 40.8 ± 33.3 mg/L, respectively). Crn excretion in urine remained unchanged after GAA administration. In conclusion, orally ingested GAA was readily bioavailable and was transformed to Cr. Serum T-Hcy kinetics proofed to be sensitive to acute GAA intake. Trial identification: clinicaltrials.gov number NCT01133899.

Patrik Drid - One of the best experts on this subject based on the ideXlab platform.

  • does dietary provision of Guanidinoacetic Acid induce global dna hypomethylation in healthy men and women
    Lifestyle genomics, 2018
    Co-Authors: Sergej M. Ostojic, Patrik Drid, Marija Mojsin, Milan Vraneš
    Abstract:

    Background/aims Guanidinoacetic Acid (GAA) is an experimental dietary additive and has been reported to induce methyl depletion when provided by the diet. However, no study evaluated whether supplemental GAA affects DNA methylation, a critical epigenetic process for genome regulation. Methods In this open-label, repeated-measure interventional trial, we evaluated the impact of 12 weeks of GAA supplementation on global DNA methylation in 14 healthy participants (8 women and 6 men, age 22.2 ± 2.3 years, body mass index 24.8 ± 5.7). Results Dietary provision of GAA had no effect on global DNA methylation, with 5-methylcytosine (m5C) nonsignificantly increased by 13.4% at postadministration when averaged across participants (95% confidence interval -5.5 to 32.3; p = 0.26). Notable DNA hypomethylation (corresponding to a 5% drop in m5C) was found in 3 of 14 participants at follow-up. Conclusion Global DNA methylation seems to be unaltered by dietary provision of 3 g of GAA per day for 12 weeks in healthy men and women.

  • dietary Guanidinoacetic Acid increases brain creatine levels in healthy men
    Nutrition, 2017
    Co-Authors: Sergej M. Ostojic, Jelena Ostojic, Patrik Drid, Milan Vraneš, Pavle Jovanov
    Abstract:

    Objective Guanidinoacetic Acid (GAA) is an experimental dietary additive that might act as a creatine source in tissues with high-energy requirements. In this case study, we evaluated brain levels of creatine in white matter, gray matter, cerebellum, and thalamus during 8 wk oral GAA administration in five healthy men and monitored the prevalence and severity of side effects of the intervention. Methods Volunteers were supplemented daily with 36 mg/kg body weight (BW) of GAA for the first 4 wk of the intervention; afterward GAA dosage was titrated ≤60 mg/kg BW of GAA daily. At baseline, 4, and 8 wk, the participants underwent brain magnetic resonance spectroscopy, clinical chemistry studies, and open-ended questionnaire for side-effect prevalence and severity. Results Brain creatine levels increased in similar fashion in cerebellum, and white and gray matter after GAA supplementation, with an initial increase of 10.7% reported after 4 wk, and additional upsurge (7.7%) from the weeks 4 to 8 follow-up (P < 0.05). Thalamus creatine levels decreased after 4 wk for 6.5% (P = 0.02), and increased nonsignificantly after 8 wk for 8% (P = 0.09). GAA induced an increase in N-acetylaspartate levels at 8-wk follow-up in all brain areas evaluated (P < 0.05). No participants reported any neurologic adverse event (e.g., seizures, tingling, convulsions) during the intervention. Conclusions Supplemental GAA led to a region-dependent increase of the creatine pool in the human brain. This might be relevant for restoring cellular bioenergetics in disorders characterized by low brain creatine and functional enzymatic machinery for creatine synthesis, including neurodegenerative diseases, brain tumors, or cerebrovascular disease.

  • a single session of exhaustive exercise markedly decreases circulating levels of Guanidinoacetic Acid in healthy men and women
    Applied Physiology Nutrition and Metabolism, 2016
    Co-Authors: Valdemar Stajer, Sergej M. Ostojic, Patrik Drid, Milan Vraneš, Tatjana Trivic
    Abstract:

    We evaluated the effects of exercise on circulating concentrations of Guanidinoacetic Acid (GAA) and creatine in 23 healthy volunteers subjected to running to exhaustion and free-weight bench-press to volitional failure. Blood was taken before and following each exercise session. Running induced a significant decrease in serum GAA by 20.1% (P < 0.001), while free-weight exercise reduced GAA by 11.7% (P < 0.001), suggesting the possible use of serum GAA as a novel biomarker of exhaustion.

  • Guanidinoacetic Acid versus creatine for improved brain and muscle creatine levels: a superiority pilot trial in healthy men
    Applied physiology nutrition and metabolism = Physiologie appliquee nutrition et metabolisme, 2016
    Co-Authors: Sergej M. Ostojic, Jelena Ostojic, Patrik Drid, Milan Vraneš
    Abstract:

    In this randomized, double-blind, crossover trial, we evaluated whether 4-week supplementation with Guanidinoacetic Acid (GAA) is superior to creatine in facilitating creatine levels in healthy men (n = 5). GAA (3.0 g/day) resulted in a more powerful rise (up to 16.2%) in tissue creatine levels in vastus medialis muscle, middle-cerebellar peduncle, and paracentral grey matter, as compared with creatine (P < 0.05). These results indicate that GAA as a preferred alternative to creatine for improved bioenergetics in energy-demanding tissues.

  • supplementation with Guanidinoacetic Acid in women with chronic fatigue syndrome
    Nutrients, 2016
    Co-Authors: Sergej M. Ostojic, Patrik Drid, Marko Stojanovic, Jay R Hoffman, Damir Sekulic, Natasa Zenic
    Abstract:

    A variety of dietary interventions has been used in the management of chronic fatigue syndrome (CFS), yet no therapeutic modality has demonstrated conclusive positive results in terms of effectiveness. The main aim of this study was to evaluate the effects of orally administered Guanidinoacetic Acid (GAA) on multidimensional fatigue inventory (MFI), musculoskeletal soreness, health-related quality of life, exercise performance, screening laboratory studies, and the occurrence of adverse events in women with CFS. Twenty-one women (age 39.3 ± 8.8 years, weight 62.8 ± 8.5 kg, height 169.5 ± 5.8 cm) who fulfilled the 1994 Centers for Disease Control and Prevention criteria for CFS were randomized in a double-blind, cross-over design, from 1 September 2014 through 31 May 2015, to receive either GAA (2.4 grams per day) or placebo (cellulose) by oral administration for three months, with a two-month wash-out period. No effects of intervention were found for the primary efficacy outcome (MFI score for general fatigue), and musculoskeletal pain at rest and during activity. After three months of intervention, participants receiving GAA significantly increased muscular creatine levels compared with the placebo group (36.3% vs. 2.4%; p < 0.01). Furthermore, changes from baseline in muscular strength and aerobic power were significantly greater in the GAA group compared with placebo (p < 0.05). Results from this study indicated that supplemental GAA can positively affect creatine metabolism and work capacity in women with CFS, yet GAA had no effect on main clinical outcomes, such as general fatigue and musculoskeletal soreness.