Effects of supplemental creatine and guanidinoacetic acid on spatial memory and the brain of weaned Yucatan miniature pigs

Abstract

The emergence of creatine as a potential cognitive enhancement supplement for humans prompted an investigation as to whether supplemental creatine could enhance spatial memory in young swine. We assessed memory performance and brain concentrations of creatine and its precursor guanidinoacetic acid (GAA) in 14-16-week-old male Yucatan miniature pigs supplemented for 2 weeks with either 200 mg/kg�d creatine (+Cr; n = 7) or equimolar GAA (157 mg/kg�d) (+GAA; n = 8) compared to controls (n = 14). Spatial memory tests had pigs explore distinct sets of objects for 5 min. Objects were spatially controlled, and we assessed exploration times of previously viewed objects relative to novel objects in familiar or novel locations. There was no effect of either supplementation on memory performance, but pigs successfully identified novel objects after 10 (p < 0.01) and 20 min (p < 0.01) retention intervals. Moreover, pigs recognized spatial transfers after 65 min (p < 0.05). Regression analyses identified associations between the ability to identify novel objects in memory tests and concentrations of creatine and GAA in cerebellum, and GAA in prefrontal cortex (p < 0.05). The concentration of creatine in brain regions was not influenced by creatine supplementation, but GAA supplementation increased GAA concentration in cerebellum (p < 0.05), and the prefrontal cortex of +GAA pigs had more creatine/g and less GAA/g compared to +Cr pigs (p < 0.05). Creatine kinase activity and maximal reaction velocity were also higher with GAA supplementation in prefrontal cortex (p < 0.05). In conclusion, there appears to be a relationship between memory performance and guanidino compounds in the cerebellum and prefrontal cortex, but the effects were unrelated to dietary supplementation. The cerebellum is identified as a target site for GAA accretion.

Effects of Dietary Guanidinoacetic Acid on the Feed Efficiency, Blood Measures, and Meat Quality of Jinjiang Bulls

“…Guanidinoacetic acid (GAA) is the only precursor of creatine (Cr) in vertebrates and can be methylated to Cr by guanidinoacetate N-methyltransferase (GAMT) (1)(2)(3)(4)(5)(6)(7)(8)(9). Cr acts as a unique energy buffer in the daily life of vertebrates (5)(6)(7)(8).…”

“…Guanidinoacetic acid (GAA) is the only precursor of creatine (Cr) in vertebrates and can be methylated to Cr by guanidinoacetate N-methyltransferase (GAMT) (1)(2)(3)(4)(5)(6)(7)(8)(9). Cr acts as a unique energy buffer in the daily life of vertebrates (5)(6)(7)(8). As a nutritive feed additive, GAA has been approved by the EFSA (European Food Safety Authority) (10,11) and the FDA (U. S. Food and Drug Administration) (12) for poultry and swine.…”

“…Spare phosphate radicals from substrate-level phosphorylation and oxidative phosphorylation tend to cause oxidative damage (2)(3)(4)(5)(6). Creatine kinases (CK) in the mitochondria and cytoplasm of somatic cells catalyze Cr and spare phosphate radicals to produce phosphocreatine (PCr) (4)(5)(6)(7)(8). PCr donates its phosphate to create ATP (adenosine triphosphate), and the resultant energy is used for body growth and various biological activities, acting as an energy buffer.…”

“…PCr donates its phosphate to create ATP (adenosine triphosphate), and the resultant energy is used for body growth and various biological activities, acting as an energy buffer. Therefore, supplementing feed with GAA is beneficial for creating Cr to reduce oxidative damage and promote feed efficiency in terms of body growth (2)(3)(4)(5)(6)(7)(8)(9)16). Moreover, Cr, which is converted from GAA, can combine with a hydrate to creatine monohydrate (CMH) or with a phosphate radical to create PCr; this enhances meat quality by binding intracellular hydrates and delaying glycolysis (1)(2)(3)(4)(5)(6)(7)(8)(9)(14)(15)(16).…”

Creatine in Health and Disease

“…Consequently, research has examined whether creatine supplementation affects cognition, memory, and/or executive function in older individuals as well as patients with mild cognitive impairment [ 94 , 168 , 174 , 177 , 178 ]. Several studies have found that creatine supplementation attenuates mental fatigue [ 27 , 28 , 127 ] and/or can improve cognition, executive function, and/or memory [ 28 , 94 , 127 , 168 , 177 , 179 ]. For example, Watanabe and associates [ 180 ] found that creatine supplementation (8 g/day for 5 days) increased oxygen utilization in the brain and reduced mental fatigue in participants performing repetitive mathematical calculations.…”