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creatine

Introduction

creatine (α-N-methylguanidine acetic acid), is a naturally occurring compound made from three amino acids: L-arginine, glycine, and L-methionine
the body primarily produces creatine in the liver, kidneys, and pancreas and hence is not an essential nutrient
plays a central role in cellular energy metabolism via its reversible conversion to phosphorylcreatine (PCr), a high-energy phosphate reservoir
creatine kinase (CK) enzyme is expressed in energy-demanding tissues, such as skeletal muscle and brain, where, via the transfer of a phosphoryl group from PCr, it facilitates rapid regeneration of adenosine triphosphate (ATP) from adenosine diphosphate (ADP)
PCr also serves as a critical spatial energy shuttle, transferring high-energy phosphates from mitochondria to cytosolic sites of ATP consumption
95% of the body's creatine is stored mainly as phosphocreatine, primarily in skeletal muscles where phosphocreatine serves as a rapid energy reserve that helps regenerate adenosine triphosphate (ATP)
creatine also supports brain health by increasing phosphocreatine stores in the brain, potentially aiding cognitive function
creatinine is a waste product formed from the breakdown of creatine and creatine phosphate

~half of daily needs are provided by dietary sources such as creatine-rich foods which include fish and meat
- endogenous synthesis of creatine may be inadequate under pathological or certain physiological conditions
- dietary supplementation is common, especially in body builders, athletes, vegetarians and those who feel it may help cognition
  - there is a risk of contamination with harmful substances if supplements are not from reputable, third-party tested sources
estimated daily requirement of creatine is about 2 g/day for a 70-kg male

in combination with resistance training, creatine supplementation may add ~1.4kg lean body mass¹⁾, but most of this may just be water retention and not add to actual strength, as CT scans show only an increased muscle thickness of only 1-2mm compared to resistance training alone²⁾
creatine raises the muscle's phosphocreatine content, helping replenish ATP quickly during short bursts of intense exercise, so you can perform more reps or lift heavier weights, which promotes muscle growth
it causes muscle cells to retain more water (cell volumization), which is an important stimulus for muscle fiber growth
can increase anabolic hormones such as IGF-1 and reduce levels of myostatin, a protein that inhibits muscle growth
helps reduce muscle protein breakdown
it effectively increases lean body mass and muscle strength especially in healthy young adults and athletes, but its benefits extend to older adults and even sedentary individuals to some degree
muscle resistance training combined with creatine supplements appear to build muscle mass more effectively than resistance training alone and may add an extra 1.4kg mass compared to no creatine supplementation ³⁾
- supplementation protocols, such as an initial loading phase of 20 g/day for 5–7 days followed by a maintenance dose of 3–5 g/day, have shown consistent benefits in enhancing muscle performance and lean mass.

theoretically, creatine supplementation may increase brain creatine and thereby support brain energetics, particularly under metabolically demanding conditions, such as sleep deprivation, hypoxia, or neurological disease⁴⁾
there is currently low certainty limited evidence from studies which suggest dietary supplementation may improve memory, attention time and processing speed
optimal supplementation regimens remain unknown and more studies are needed to ascertain if this is real and in which sub groups would benefit the most (eg. aging adults may be have the most benefit)

on going intakes of over 3-5g/day after the initial loading doses may cause a range of adverse effects
gastrointestinal issues such as diarrhea, stomach upset, nausea, and cramps, especially with large single doses
weight gain due primarily to water retention in muscles (cell volumization), which may cause bloating
potential dehydration and electrolyte imbalances if fluid intake is inadequate during supplementation
anxiety, headaches, fever, and fatigue
may be an issue for those taking diuretics or who have hypertension, bipolar disorder, kidney or liver problems

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