Research Letter

Guanidinoacetic acid increases skeletal muscle creatine stores in healthy men

The current study was carried out to detect the effect of dietary guanidinoacetic acid (GAA) supplementation on carcass characteristics and meat quality in finishing pigs fed different dietary crude protein (CP) levels. Sixty-four barrows with an initial body weight of 73.05 ± 2.34 kg were randomly allocated into 1 of 4 dietary treatments in a 2 (100% vs. 125% NRC CP level) × 2 (0 vs. 300 mg/kg GAA) factorial arrangement (n = 7). The feeding trial lasted for 49 d. GAA supplementation significantly reduced drip loss (P = 0.01), free water distribution (T₂₃ peak area ratio) (P = 0.05) and the concentrations of free alanine, threonine, methionine and isoleucine (P < 0.05); but increased total glycine content (P = 0.03) in the longissimus dorsi muscle of finishing pigs regardless of the dietary CP levels. Furthermore, primary myogenic cell differentiation system was employed to investigate the influence of inclusion of GAA on free amino acid concentrations in myotubes (n = 4) and validate the finding in the animal feeding trial. We found that GAA inclusion in culture medium also decreased intracellular concentrations of free alanine, threonine, methionine, isoleucine, valine and proline in differentiated primary myogenic cells in vitro (P < 0.05). Meanwhile, relative to diets with 100% NRC CP level, the intake of diets with 125% NRC CP level improved sarcoplasmic protein solubility, increased the contents of carnosine and total free amino acids as well as flavor amino acids in the longissimus dorsi muscle and decreased backfat thickness at the 6–7th ribs in pigs (P < 0.05). In addition, we observed that the impact of dietary GAA supplementation on the last rib fat thickness, shear force, and free lysine content in the longissimus dorsi muscle was dependent on dietary CP levels (P < 0.05). Collectively, dietary GAA supplementation can reduce drip loss, decrease the concentrations of free amino acids and flavor amino acids of fresh meat independent of dietary CP levels.

In this study, we investigated the effects of guanidinoacetic acid (GAA) and betaine (BT) on growth performance, nutrient digestion, energy-nitrogen metabolism, and microbial protein synthesis in lambs. Forty-eight 3-month-old Dorper × Thin-tailed Han first crossbred generation ram lambs with similar body weight (22.03 ± 1.3 kg; mean ± SD) were randomly divided into 4 groups. According to the 2 × 2 factorial arrangement, lambs in each of the 4 groups were fed basal diets, or basal diets supplemented with 0.9 g GAA/kg dietary dry matter (DM), 5 g BT/day, or 5 g BT/day + 0.9 g GAA/kg dietary DM. Before the formal trial, all lambs were allowed to adapt to the facilities as well as the basal diet for 15 days. This study lasted for 71 days including a 60-day period for feeding trial and an 11-day period for digestion and metabolism trials. The results showed that supplementation with GAA or BT increased the average daily gain (ADG) and feed efficiency (FE). However, no further increase in ADG or FE was observed with the combination of GAA and BT compared to that induced by addition of GAA or BT alone. Moreover, the addition of GAA or BT improved the apparent digestibility of dry matter (DM) and neutral detergent fiber (NDF), while GAA increased acid detergent fiber (ADF). GAA or BT supplementation decreased ruminal pH but increased the concentration of total volatile fatty acids (T-VFA), propionate, and valerate. Ruminal ammonia N content was not influenced by GAA or BT supplementation. Addition of GAA or BT resulted in an increase in microbial protein (MCP) synthesis. Additionally, supplementation with GAA or BT promoted digestible nitrogen (N), retained N, digestible energy and apparent digestibility of gross energy, and reduced fecal N. Supplementation with GAA decreased urinary N and increased metabolizable energy. The addition of GAA or BT increased total protein and creatine levels in serum, but the addition of BT alone decreased blood homocysteine (Hcy) levels. GAA elevated blood insulin-like growth factors-1 (IGF-1). These results demonstrate that supplementation with GAA or BT improves growth performance, nutrient digestibility, and energy-nitrogen metabolism, but the addition of BT and GAA in combination does not further improve the growth of lambs.

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.

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.

A confined absorption of exogenous creatine through creatine transporter (CRT1) seems to hamper its optimal uptake in bioenergetical deficits. Co-administration of guanidinoacetic acid (GAA) along with creatine could target other transport channels besides CRT1, and supremely improve cellular levels of creatine. This innovative approach might tackle tissues difficult to reach with conventional creatine interventions, providing a potentially more effective and safe mixture in clinical pharmacology and therapeutics.

Tissues with high-energy output, such as the brain and skeletal muscle, suffer the most from impaired or depleted energy levels, with innovative nutritional approaches needed to effectively tackle metabolic deficits in bioenergetics. Here, we highlight the role of guanidinoacetic acid in the control and provision of cellular energy by its interaction with cellular transporters for taurine (SLC6 A6) and γ-aminobutyric acid (SLC6 A13), previously dismissed as “untargetable” carriers by other bioenergetics therapeutics.