Guanidinop Proprionic Acid
Also known as: β-GPA, Guanidinopropionic acid, beta-GPA, Beta-guanidinopropionic acid
Overview
Beta-guanidinopropionic acid (β-GPA) is a naturally occurring creatine analogue that functions as a metabolic modulator. It primarily acts by competitively inhibiting cellular creatine uptake and the activity of creatine kinase (CK), an enzyme crucial for cellular energy metabolism. This inhibition forces cells, particularly in high-energy demand tissues like skeletal muscle, heart, and brain, to shift their energy production from glycolytic to oxidative pathways. Research, predominantly in animal models, indicates that β-GPA can enhance fatigue resistance in muscle, improve survival under ischemic conditions, and induce metabolic adaptations. While it holds promise as a dietary supplement candidate, human data are limited, with most evidence derived from preclinical studies and early-phase research protocols.
Benefits
β-GPA's primary benefits, observed mainly in animal models, stem from its ability to induce a metabolic shift. It decreases intracellular creatine and phosphocreatine levels, compelling skeletal muscle to rely more on oxidative metabolism. This leads to increased fatigue tolerance and enhanced glucose uptake in muscle tissue, as supported by systematic reviews of animal studies. Furthermore, animal research indicates that β-GPA can enhance ATP stability and improve survival during hypoxic conditions in brain tissue. While it may cause a modest reduction in myocardial contractility, cardiac output remains stable in animal studies. Secondary effects in young rodents include reductions in body and fat mass and the promotion of smaller, more oxidative muscle fibers, suggesting improved metabolic function. In older animals, β-GPA may help prevent lean mass loss. However, it is crucial to note that these benefits are currently limited to animal models, and there is no confirmed human efficacy data.
How it works
Beta-guanidinopropionic acid (β-GPA) exerts its effects by acting as a competitive inhibitor of creatine uptake and creatine kinase (CK) activity. This disruption interferes with the phosphocreatine shuttle, which is vital for buffering ATP levels within cells. By reducing intracellular creatine and phosphocreatine concentrations, β-GPA forces cells to decrease their reliance on glycolysis and instead increase their dependence on mitochondrial oxidative phosphorylation. This metabolic shift leads to enhanced glucose uptake and overall oxidative metabolism. Additionally, β-GPA is known to activate AMP-activated protein kinase (AMPK), a key energy sensor that plays a role in promoting mitochondrial biogenesis and facilitating metabolic adaptation within cells. The bioavailability and pharmacokinetics in humans are not yet well-characterized, with most mechanistic insights derived from chronic oral administration in animal studies.
Side effects
Animal studies generally report β-GPA as safe at tested doses, with no major adverse effects. A modest reduction in myocardial contractility has been observed in animals, but cardiac output remained stable. However, human safety data are largely lacking, and while it is marked as safe for human use in some contexts, clinical validation is required. Due to the absence of extensive human clinical trials, there are no reported common or rare side effects in humans. The potential for drug interactions is currently unknown, and caution is advised given its significant effects on energy metabolism and cardiac function. Individuals with pre-existing cardiac conditions or those taking medications that affect metabolism or heart function should exercise extreme caution and consult a healthcare professional before considering β-GPA, as its full safety profile in humans is yet to be established.
Dosage
There are no established human dosing guidelines for Beta-guanidinopropionic acid (β-GPA) due to the lack of completed clinical trials in humans. Animal studies typically utilize chronic oral doses ranging from 0.5% to 3.5% of the diet, which translates to several hundred milligrams per kilogram of body weight per day. However, these animal dosages cannot be directly extrapolated to humans without proper clinical research. The optimal timing of administration, specific formulations, and factors influencing bioavailability in humans remain undefined. Without human clinical data, any dosage recommendations would be speculative and potentially unsafe. Therefore, β-GPA should not be used in humans until robust clinical trials establish safe and effective dosing parameters.
FAQs
Is β-GPA effective in humans?
No conclusive human efficacy data exist. Current evidence is primarily from animal studies and early-phase research protocols, with no completed human clinical trials demonstrating effectiveness.
Is β-GPA safe for human consumption?
While animal studies suggest it is generally safe, human safety has not been established through clinical trials. Caution is advised, and human use requires further clinical validation.
How does β-GPA compare to creatine?
Unlike creatine, which buffers ATP, β-GPA inhibits creatine uptake and creatine kinase activity. This leads to a metabolic shift towards oxidative pathways rather than direct energy buffering.
What results can be expected from β-GPA?
In animal models, β-GPA has shown improved muscle fatigue resistance and metabolic adaptations. However, its effects and benefits in humans are currently unknown and require further research.
Research Sources
- https://pubmed.ncbi.nlm.nih.gov/23326362/ – This systematic review of 131 animal studies on β-GPA found that it consistently decreases creatine/phosphocreatine levels, shifts cellular metabolism towards oxidative pathways, and increases fatigue tolerance in various tissues. It also noted modest cardiac effects but maintained stable cardiac output. The review highlights the lack of human data.
- https://journals.plos.org/plosone/article/file?type=printable&id=10.1371%2Fjournal.pone.0052879 – This source, likely the full text of the Oudman et al. 2013 systematic review, details the comprehensive findings on β-GPA's metabolic effects in animal models. It emphasizes the compound's ability to induce a metabolic shift and improve fatigue resistance by altering creatine metabolism, while also discussing its impact on cardiac function.
- https://www.bohrium.com/paper-details/the-acute-effect-of-beta-guanidinopropionic-acid-versus-creatine-or-placebo-in-healthy-men-abc-trial-study-protocol-for-a-randomized-controlled-trial/814653403253702656-7237 – This entry describes the protocol for a planned human randomized controlled trial (ABC trial) designed to investigate the acute effects of β-GPA on blood pressure and energy metabolism in healthy men. It outlines the methodology for a future study, but no results are yet available.
- https://pmc.ncbi.nlm.nih.gov/articles/PMC8190243/ – This animal RCT investigated the effects of chronic β-GPA administration in young and old mice. It found that β-GPA reduced body and fat mass in young animals and helped preserve lean mass in older males, suggesting age-specific metabolic benefits and activation of AMPK. The study provides evidence for metabolic adaptations in an animal model.
- https://ui.adsabs.harvard.edu/abs/2013PLoSO...852879O/abstract – This abstract likely refers to the Oudman et al. (2013) systematic review published in PLoS ONE. It summarizes the key findings that β-GPA decreases creatine/phosphocreatine levels, shifts metabolism to oxidative pathways, and increases fatigue tolerance in animal models, while noting the absence of human clinical data.