Creatine has been shown before in vitro to protect from MPTP-induced toxicity, which targets dopaminergic neurons in the substantia nigra and induce Parkinson’s disease in research animals.[235] Creatine also protected these cells from death induced by low oxygen or glucose.[574] One study noted that dopaminergic cell survival under the influence of creatine was 1.32-fold higher than control cells, the soma (cell body) was enlarged by 1.12-fold in these cells,[574] and creatine showed some growth-enhancing effects while helping reducing destruction of dopaminergic neurons by various insults.[574]
If you’re exercising at your maximum intensity, your body literally can’t produce enough ATP to keep up. (10) That’s where creatine supplements come in: They can help increase your body’s stores of phosphocreatine (an organic compound of creatine and phosphoric acid that’s stored in your muscle tissue) to produce new ATP during high-intensity exercise.
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In regard to carbohydrate oxidation during exercise, it appears that rats subject to intermittent physical exercise (which utilizes glycogen) have decreased lactate production during said exercise, suggesting a preservation of glycogen usage. This occurred alongside an increase in glycogen stores.[359] This is thought to be due to phosphocreatine donating phosphate to replenish ATP. Without any changes in whole body metabolic rate, it indirectly causes less glucose to be required to replenish ATP, due to a quota needing to be met during exercise and creatine phosphate taking up a relatively larger percentage of said quota.

In vitro, creatine (0.125mM or higher) can reduce excitotoxicity from glutamate, which is thought to be secondary to preserving intracellular creatine phosphate levels.[209] Glutamate-induced excitotoxicity is caused by excessive intracellular calcium levels resulting from ATP depletion. Since high levels of calcium inside the cell are toxic, ATP preserves membrane integrity,[210] in part by promoting calcium homeostasis. When ATP is depleted, the sodium-potassium ATPase pump (Na+,K+-ATPase) stops working, leading to sodium accumulation in the cell. This reduces the activity of the sodium-calcium exchange pump, which, alongside a lack of ATP, reduces calcium efflux through the Na+,K+-ATPase. Thus, ATP depletion leads to intracellular calcium overload, loss of membrane potential, and excitotoxic cell death. Therefore, by helping preserve ATP levels, creatine is protective against excitotoxicity. This protective effect was noted after either creatine preloading or addition up to 2 hours after excitotoxicity.[209] Protection from glutamate-induced toxicity also extends to glial cells[211] and is additive with COX2 inhibition.[212]


Injections of creatine are known to be neuroprotective against low oxygen levels (hypoxia) even to neonatal rats.[532] This is thought to be associated with the increased collective pool of phosphocreatine and creatine.[236] Since oral ingestion of creatine by the mother increases brain concentrations of creatine by 3.6% in the fetus prior to birth,[531] it is thought to be protective in the fetuses subject to hypoxic (low oxygen) stressors, such as a caesarean section.

In contrast to the above null effects, ingestion of creatine both before and after a workout (alongside protein and carbohydrate) over 10 weeks seems to promote muscle growth more than the same supplement taken in the morning, farther away from the time of the workout.[386] The benefits of creatine around the workout, relative to other times, have been hypothesized[387] to be related to an upregulation of creatine transport secondary to muscle contraction, a known phenomena.[153]
Sandow was so successful at flexing and posing his physique that he later created several businesses around his fame, and was among the first to market products branded with his name. He was credited with inventing and selling the first exercise equipment for the masses: machined dumbbells, spring pulleys, and tension bands. Even his image was sold by the thousands in "cabinet cards" and other prints. Sandow was a perfect "Gracilian", a standard of ideal body proportions close to those of ancient Greek and Roman statues. Men's physiques were then judged by how closely they matched these proportions. 
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