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Creatine supplementation during pregnancy: summary of experimental studies suggesting a treatment to improve fetal and neonatal morbidity and reduce mortality in high-risk human pregnancy.

Dickinson H, Ellery S, Ireland Z, LaRosa D, Snow R, Walker DW - BMC Pregnancy Childbirth (2014)

Bottom Line: While the use of creatine in human pregnancy is yet to be fully evaluated, its long-term use in healthy adults appears to be safe, and its well documented neuroprotective properties have recently been extended by demonstrations that creatine improves cognitive function in normal and elderly people, and motor skills in sleep-deprived subjects.Creatine has many actions likely to benefit the fetus and newborn, because pregnancy is a state of heightened metabolic activity, and the placenta is a key source of free radicals of oxygen and nitrogen.In the brain, creatine not only reduces lipid peroxidation and improves cerebral perfusion, its interaction with the benzodiazepine site of the GABAA receptor is likely to counteract the effects of glutamate excitotoxicity - actions that may protect the preterm and term fetal brain from the effects of birth hypoxia.

View Article: PubMed Central - HTML - PubMed

Affiliation: The Ritchie Centre, MIMR-PHI Institute of Medical Research, Monash University, 27-31 Wright St,, Clayton, Melbourne 3168 Australia. david.walker@monash.edu.

ABSTRACT
While the use of creatine in human pregnancy is yet to be fully evaluated, its long-term use in healthy adults appears to be safe, and its well documented neuroprotective properties have recently been extended by demonstrations that creatine improves cognitive function in normal and elderly people, and motor skills in sleep-deprived subjects. Creatine has many actions likely to benefit the fetus and newborn, because pregnancy is a state of heightened metabolic activity, and the placenta is a key source of free radicals of oxygen and nitrogen. The multiple benefits of supplementary creatine arise from the fact that the creatine-phosphocreatine [PCr] system has physiologically important roles that include maintenance of intracellular ATP and acid-base balance, post-ischaemic recovery of protein synthesis, cerebral vasodilation, antioxidant actions, and stabilisation of lipid membranes. In the brain, creatine not only reduces lipid peroxidation and improves cerebral perfusion, its interaction with the benzodiazepine site of the GABAA receptor is likely to counteract the effects of glutamate excitotoxicity - actions that may protect the preterm and term fetal brain from the effects of birth hypoxia. In this review we discuss the development of creatine synthesis during fetal life, the transfer of creatine from mother to fetus, and propose that creatine supplementation during pregnancy may have benefits for the fetus and neonate whenever oxidative stress or feto-placental hypoxia arise, as in cases of fetal growth restriction, premature birth, or when parturition is delayed or complicated by oxygen deprivation of the newborn.

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Creatine is an amino acid derivative involved with cellular energy production. In the form of energetically charged phosphocreatine (PCr), its primary function is to provide the phosphate group for regeneration of ATP from ADP in tissues of high and fluctuating energy demands. Human adults obtain approximately half of their daily requirement for creatine from a diet containing fresh fish, meat, and other animal products. The remainder is synthesized endogenously from arginine, glycine and methionine (methyl donor for GAMT reaction). This is a two-step process involving arginine:glycine aminotransferase (AGAT), principally in the kidney, producing guanidinoacetate (GAA), followed by hepatic guanidinoacetate methyltransferase (GAMT) activity producing creatine. Once synthesized, creatine is released from the liver into the circulation and taken up by most tissues, particularly muscle, by means of the creatine transporter. Inside the tissues a proportion of the creatine is phosphorylated to PCr, via the action of creatine kinase (CK). One important aspect of creatine biosynthesis is that the daily utilization of methyl groups on the GAMT reaction roughly equals the total daily intake of ‘labile’ methyl groups (methionine + choline) in an average diet. Thus, if methionine and choline levels are reduced, then endogenous creatine biosynthesis, responsible for half of our daily requirement for creatine, may be critically reduced.
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Figure 1: Creatine is an amino acid derivative involved with cellular energy production. In the form of energetically charged phosphocreatine (PCr), its primary function is to provide the phosphate group for regeneration of ATP from ADP in tissues of high and fluctuating energy demands. Human adults obtain approximately half of their daily requirement for creatine from a diet containing fresh fish, meat, and other animal products. The remainder is synthesized endogenously from arginine, glycine and methionine (methyl donor for GAMT reaction). This is a two-step process involving arginine:glycine aminotransferase (AGAT), principally in the kidney, producing guanidinoacetate (GAA), followed by hepatic guanidinoacetate methyltransferase (GAMT) activity producing creatine. Once synthesized, creatine is released from the liver into the circulation and taken up by most tissues, particularly muscle, by means of the creatine transporter. Inside the tissues a proportion of the creatine is phosphorylated to PCr, via the action of creatine kinase (CK). One important aspect of creatine biosynthesis is that the daily utilization of methyl groups on the GAMT reaction roughly equals the total daily intake of ‘labile’ methyl groups (methionine + choline) in an average diet. Thus, if methionine and choline levels are reduced, then endogenous creatine biosynthesis, responsible for half of our daily requirement for creatine, may be critically reduced.

Mentions: The synthesis of creatine and its availability in a diet containing meat, milk products and fish is shown in Figure 1. Human adults obtain approximately half of their daily requirement for creatine from a diet containing meat, fish and other animal products, the remainder being synthesized endogenously from arginine, glycine and methionine in a two-step process involving arginine:glycine aminotransferase (AGAT), principally in the kidney, followed by hepatic methylation via guanidinoacetate methyltransferase (GAMT). Creatine is then released from the liver into the circulation and taken up by most tissues, especially muscle, by means of the creatine transporter protein (CrT). Once inside the tissues a proportion of the creatine is phosphorylated to form phosphocreatine via the action of creatine phosphokinase. Despite this endogenous synthesis, ingesting creatine increases the creatine content of skeletal muscle [15] and brain [16] indicating that in healthy people the intracellular pool of creatine is not fully saturated.


Creatine supplementation during pregnancy: summary of experimental studies suggesting a treatment to improve fetal and neonatal morbidity and reduce mortality in high-risk human pregnancy.

Dickinson H, Ellery S, Ireland Z, LaRosa D, Snow R, Walker DW - BMC Pregnancy Childbirth (2014)

Creatine is an amino acid derivative involved with cellular energy production. In the form of energetically charged phosphocreatine (PCr), its primary function is to provide the phosphate group for regeneration of ATP from ADP in tissues of high and fluctuating energy demands. Human adults obtain approximately half of their daily requirement for creatine from a diet containing fresh fish, meat, and other animal products. The remainder is synthesized endogenously from arginine, glycine and methionine (methyl donor for GAMT reaction). This is a two-step process involving arginine:glycine aminotransferase (AGAT), principally in the kidney, producing guanidinoacetate (GAA), followed by hepatic guanidinoacetate methyltransferase (GAMT) activity producing creatine. Once synthesized, creatine is released from the liver into the circulation and taken up by most tissues, particularly muscle, by means of the creatine transporter. Inside the tissues a proportion of the creatine is phosphorylated to PCr, via the action of creatine kinase (CK). One important aspect of creatine biosynthesis is that the daily utilization of methyl groups on the GAMT reaction roughly equals the total daily intake of ‘labile’ methyl groups (methionine + choline) in an average diet. Thus, if methionine and choline levels are reduced, then endogenous creatine biosynthesis, responsible for half of our daily requirement for creatine, may be critically reduced.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4007139&req=5

Figure 1: Creatine is an amino acid derivative involved with cellular energy production. In the form of energetically charged phosphocreatine (PCr), its primary function is to provide the phosphate group for regeneration of ATP from ADP in tissues of high and fluctuating energy demands. Human adults obtain approximately half of their daily requirement for creatine from a diet containing fresh fish, meat, and other animal products. The remainder is synthesized endogenously from arginine, glycine and methionine (methyl donor for GAMT reaction). This is a two-step process involving arginine:glycine aminotransferase (AGAT), principally in the kidney, producing guanidinoacetate (GAA), followed by hepatic guanidinoacetate methyltransferase (GAMT) activity producing creatine. Once synthesized, creatine is released from the liver into the circulation and taken up by most tissues, particularly muscle, by means of the creatine transporter. Inside the tissues a proportion of the creatine is phosphorylated to PCr, via the action of creatine kinase (CK). One important aspect of creatine biosynthesis is that the daily utilization of methyl groups on the GAMT reaction roughly equals the total daily intake of ‘labile’ methyl groups (methionine + choline) in an average diet. Thus, if methionine and choline levels are reduced, then endogenous creatine biosynthesis, responsible for half of our daily requirement for creatine, may be critically reduced.
Mentions: The synthesis of creatine and its availability in a diet containing meat, milk products and fish is shown in Figure 1. Human adults obtain approximately half of their daily requirement for creatine from a diet containing meat, fish and other animal products, the remainder being synthesized endogenously from arginine, glycine and methionine in a two-step process involving arginine:glycine aminotransferase (AGAT), principally in the kidney, followed by hepatic methylation via guanidinoacetate methyltransferase (GAMT). Creatine is then released from the liver into the circulation and taken up by most tissues, especially muscle, by means of the creatine transporter protein (CrT). Once inside the tissues a proportion of the creatine is phosphorylated to form phosphocreatine via the action of creatine phosphokinase. Despite this endogenous synthesis, ingesting creatine increases the creatine content of skeletal muscle [15] and brain [16] indicating that in healthy people the intracellular pool of creatine is not fully saturated.

Bottom Line: While the use of creatine in human pregnancy is yet to be fully evaluated, its long-term use in healthy adults appears to be safe, and its well documented neuroprotective properties have recently been extended by demonstrations that creatine improves cognitive function in normal and elderly people, and motor skills in sleep-deprived subjects.Creatine has many actions likely to benefit the fetus and newborn, because pregnancy is a state of heightened metabolic activity, and the placenta is a key source of free radicals of oxygen and nitrogen.In the brain, creatine not only reduces lipid peroxidation and improves cerebral perfusion, its interaction with the benzodiazepine site of the GABAA receptor is likely to counteract the effects of glutamate excitotoxicity - actions that may protect the preterm and term fetal brain from the effects of birth hypoxia.

View Article: PubMed Central - HTML - PubMed

Affiliation: The Ritchie Centre, MIMR-PHI Institute of Medical Research, Monash University, 27-31 Wright St,, Clayton, Melbourne 3168 Australia. david.walker@monash.edu.

ABSTRACT
While the use of creatine in human pregnancy is yet to be fully evaluated, its long-term use in healthy adults appears to be safe, and its well documented neuroprotective properties have recently been extended by demonstrations that creatine improves cognitive function in normal and elderly people, and motor skills in sleep-deprived subjects. Creatine has many actions likely to benefit the fetus and newborn, because pregnancy is a state of heightened metabolic activity, and the placenta is a key source of free radicals of oxygen and nitrogen. The multiple benefits of supplementary creatine arise from the fact that the creatine-phosphocreatine [PCr] system has physiologically important roles that include maintenance of intracellular ATP and acid-base balance, post-ischaemic recovery of protein synthesis, cerebral vasodilation, antioxidant actions, and stabilisation of lipid membranes. In the brain, creatine not only reduces lipid peroxidation and improves cerebral perfusion, its interaction with the benzodiazepine site of the GABAA receptor is likely to counteract the effects of glutamate excitotoxicity - actions that may protect the preterm and term fetal brain from the effects of birth hypoxia. In this review we discuss the development of creatine synthesis during fetal life, the transfer of creatine from mother to fetus, and propose that creatine supplementation during pregnancy may have benefits for the fetus and neonate whenever oxidative stress or feto-placental hypoxia arise, as in cases of fetal growth restriction, premature birth, or when parturition is delayed or complicated by oxygen deprivation of the newborn.

Show MeSH
Related in: MedlinePlus