Recent publications by Verhelle und Saremi (2024) and Westreicher-Kristen et al. (2025) reported broiler feeding experiments to evaluate the nutritional value of guanidinoacetic acid (GAA) in comparison to L-arginine (L-Arg). Basically, reported broiler performance responses are in agreement with expectations based on literature. However, the authors drew misleading conclusions on the efficacy of GAA. It is our objective to clarify this matter because both publications confirm high arginine sparing potential of guanidinoacetic acid which can result in substantial economic advantages if applied in feed formulation.

Guanidinoacetic acid and L-arginine were compared in a simultaneous dose-response assay

Verhelle und Saremi (2024) reported a broiler feeding experiment addressing the nutritional value of guanidinoacetic acid (GAA) in comparison to L-arginine (L-Arg). The trial followed a classical simultaneous dose-response approach including an Arg-deficient basal diets which was supplemented with graded levels 0.06, 0.12, 0.18, 0.30, 0.45 and 0.61 % of either L-Arg or GAA, respectively. However, conclusions derived from the broiler responses must be related to physiological aspects of GAA and L-Arg which – a priori – would define the expectations.

Arginine is an essential amino acid in broiler nutrition. It not only has a meaning as building block for protein synthesis but also has an important involvement in immune responses, fertility and vasodilation (Khajali und Wideman 2010; Izadi Yazdanabadi et al. 2025). Moreover, Arg is one amino acid needed for de-novo synthesis of GAA and, therefore, supplementation of GAA to feed can spare Arg for de-novo synthesis (Khajali et al. 2020; Portocarero und Braun 2021; Dao und Swick 2021). From this metabolic relationship between GAA and Arg, it can be concluded that GAA can only spare that amount of Arg which would be needed for de-novo GAA and creatine formation (Khajali et al. 2020). Moreover, the Arg-sparing potential of 600 g/t GAA ranges between 77% and 149% (Khajali et al. 2020). This means, one unit of supplemental GAA is worth 0.77 to 1.49 units of dietary arginine. The large range depends on the severity of Arg deficiency in the diet or, in other words, the magnitude of gap between dietary Arg and the Arg requirement of the animal on the one hand, (Dao und Swick 2021; Khajali et al. 2020). On the other hand, sparing potential of > 100 percent is possible because GAA (117.11 g/M) and Arg (174.20 g/M) differ in their molecular weight and in this context one molecule GAA could spare one molecule Arg (174.20 / 117.11 = 149%) (Dao und Swick 2021; Khajali et al. 2020). GAA supplementation to broiler feed basically increases muscle creatine content (Khajali et al. 2020). However, it could be demonstrated that supplemental GAA is 3-fold more efficient to increase muscle creatine levels than supplementing L-Arg (Portocarero und Braun 2021; DeGroot et al. 2018). This indicates that GAA is the most efficient metabolic precursor of creatine and can reduce the need of endogenous GAA synthesis and thereby can spare Arg.

Accordingly, increasing doses of dietary GAA would only be successful until the demand for de-novo synthesis of GAA and creatine is met. Higher levels of supplemental GAA can therefore not have further beneficial effects as nicely demonstrated with the data by Verhelle und Saremi (2024). Moreover, the European feed legislation allows 600 to 1200 g/t GAA while higher levels are not allowed (European Commission 2016). Consequently, higher levels would be seen as overdose (EFSA 2016). Therefore, it is not surprising that supplementation levels of 4500 or 6100 g/t GAA in the trial by Verhelle und Saremi (2024) resulted in a decline of broiler performance.

Results reported by Verhelle and Saremi (2024) suggest an arginine sparing potential of guanidinoacetic acid of up to 97%.

Recent publications demonstrate arginine sparing potential of guanidinoacetic acid - Image 1

Click here to enlarge the image

Supplementation of particularly 600 to 1200 g/t GAA to the Arg-deficient resulted in performance improvements (Verhelle und Saremi 2024). In fact, supplementation of 600 g/t GAA resulted in almost same overall growth performance than 600 g/t L-Arg suggesting a 100% Arg-sparing potential for GAA and is, thus, confirming the findings summarized by others (Portocarero und Braun 2021; Khajali et al. 2020; Dao und Swick 2021). Also, overall FCR was identical between GAA and L-Arg treatments (Figure 1) while other performance indicators were also similar at 1200 g /t GAA leading to the same conclusion on Arg-sparing potential as for 600 g/t. Verhelle und Saremi (2024) claimed they would first time publish a bioefficacy study based on a dose-response trial. However, due to the above-mentioned mode of action of GAA concerning Arg sparing, there are limits for a reliable bioefficacy study in a direct comparison. According to Verhelle und Saremi’s (2024) analysis - using a non-established approach comparing the outcome of different regression models applied for the L-Arg and GAA dose-responses (Figure 1) – GAA was 57% and 78% as efficient as L-Arg concerning weight gain and feed conversion ratio. By the way, the latter being in line with the lower Arg-sparing potential reported by Khajali et al. (2020). However, a simplified slope-ratio approach within the range of permitted doses of GAA up to 1200 g/t (European Commission) suggests GAA to be 77% or 97% as efficient as L-Arg to achieve same body weight or feed conversion ratio, respectively (Figure 2). In other words, GAA had an Arg sparing potential of 77 to 97% without compromising broiler growth or feed conversion ratio within these recommended dosages of GAA.

Recent publications demonstrate arginine sparing potential of guanidinoacetic acid - Image 3

Click here to enlarge the image

A high Arg-sparing potential of guanidinoacetic acid has been impressively confirmed

In a further recent publication, also co-authored by Dr. Saremi, the concept of Arg-sparing potential of GAA was tested in broilers (Westreicher-Kristen et al. 2025). In brief, positive control diets were formulated to meet optimal amino acid levels in a 4-phase feeding program up to 44 days. In a second treatment 77% Arg-sparing potential was applied while in treatment three 149% Arg-sparing was applied which means 600 g supplemented GAA replaced 462 g (600 x 0.77) or 894 g Arg (600 x 1.49) in feed formulation, respectively. In both cases also 50 kcal metabolizable energy sparing was considered for GAA as well. All positive control diets contained 470 g/t L-Arg. Details on the GAA-diet formulations are missing in the paper but in a technical bulletin by Saremi (2022) at least starter diets of this trial were shared. Accordingly, 77% Arg-sparing applied for GAA replaced L-Arg completely without affecting the diet formulation drastically. Only oil addition was reduced by 46%. However, assuming 149% Arg-sparing for GAA not only completely replaced L-Arg but also affected diet composition resulting in lower wheat and soybean meal inclusion and higher corn inclusion. In addition, corn gluten meal was introduced, and oil addition was reduced to 0.355% (20% of positive control). These changes should reduce diet cost by about 5 €/t or 10 €/t in the 77% or 149% Arg-sparing GAA treatments. Analysed Arg levels in the 77% and 149% Arg sparing treatments were reduced compared to control feed confirming that 0.06% GAA replaced 0.046% and 0.089% Arg in the feed.

Click here to enlarge the image

Broiler performance in this 44-day trial did not differ between all three treatments neither concerning growth and feed conversion ratio nor concerning carcass evaluation - actually significant higher breast meat yield was observed at 35 days of age. (Figure 3; Westreicher-Kristen et al. 2025). This result impressively demonstrates that GAA successfully spared Arg. In addition, analysed dietary Arg levels in the 149% Arg sparing treatments represented rather low digestible Arg to digestible Lys ratios of 98 to 99% in the 4-phase feeding trial suggesting marginal dietary Arg supply. Therefore, the publication provided strong evidence that an Arg-sparing potential of up to 149% by 600 g GAA supplementation per ton of feed is possible (Westreicher-Kristen et al. 2025). Moreover, considerable cost savings should have been realized with the GAA treatments compared to the positive control.

In conclusion, the trial setup and respective results by Verhelle und Saremi (2024) allowed for determining an optimal dietary Arg level by means of regression analysis. It is not advisable to perform a dose-response assay with GAA including dosages well above 1200 g/t because GAA is not a direct Arg source but has Arg-sparing potential which is defined by avoiding using dietary Arg for de-novo GAA formation with GAA supplementation. However, the use of Arg for the de-novo synthesis of GAA is tightly regulated by metabolic creatine levels due to a negative feedback mechanism suppressing the activity of the key enzyme L-Arginine:glycine amidinotransferase (Khajali et al. 2020). Therefore, Arg use for GAA synthesis is limited by this feedback mechanism and Arg-sparing of GAA is limited likewise. At recommended doses of GAA, the trial by Verhelle und Saremi (2024) revealed Arg sparing potential of up to 97% while research by Westreicher-Kristen et al. (2025) provides evidence for the applicability of Arg- and AME-sparing potentials for GAA in broiler feeds and actually confirms 149% Arg-sparing potential in this trial.

Final remark to Westreicher-Kristen et al. (2025) concerning meat myopathies

While growth performance, feed conversion ratio and carcass evaluation did not suggest any negative impact of GAA supplementation, the authors pronounce that use of GAA particularly at 149% Arg-sparing would result in in higher occurrence of meat myopathies such as severe woody breast and spaghetti meat. First, statistically, the values reported are far away from being significant. Second, the values of 16.7% and 4.17% as reported for woody breast and spaghetti meat in 42-day old broilers represent 4 and 1 fillet of the overall samples indicating that the conclusions by Westreicher-Kristen et al. (2025) are based on a very little number of cases. Moreover, although also samples taken at days 28 and 35 were examined, only results for 42 days was reported. Therefore, conclusions by Westreicher-Kristen et al. (2025) are not justified. Actually, the contrary has been reported: Córdova-Noboa et al. (2018) and Maynard et al. (2023) provided strong evidence that supplemental GAA decreased the prevalence of particularly severe cases of woody breast and white striping in broilers.

Recent publications demonstrate arginine sparing potential of guanidinoacetic acid

GuanAMINO®