Minor liver lesions (grade I, no grade II or III, pathology not indicative of toxicity) have been studied in SOD1 G93A transgenic mice (a research model for amyotrophic lateral sclerosis or ALS, but used in this study to assess a state of chronic pro-oxidative stress) for 159 days with 2% of feed intake and in CD-1 rats (seen as normal) over 56 days with 0.025-0.5mg/kg in CD-1 mice, although in Sprague-Dawley rats (normal controls) there were no significant differences noted even after 2% of feed intake for 365 days. These observations appear to be due to the strain of the rodents used, and human studies on amyotrophic lateral sclerosis (ALS; what the SOD1 G93A transgenic mice are thought to represent) lasting from nine to sixteen months with subjects supplementing with up to 10g of creatine daily have failed to find any abnormalities in serum biomarkers of liver or kidney health.
Bird, L. M., Tan, W. H., Bacino, C. A., Peters, S. U., Skinner, S. A., Anselm, I., Barbieri-Welge, R., Bauer-Carlin, A., Gentile, J. K., Glaze, D. G., Horowitz, L. T., Mohan, K. N., Nespeca, M. P., Sahoo, T., Sarco, D., Waisbren, S. E., and Beaudet, A. L. A therapeutic trial of pro-methylation dietary supplements in Angelman syndrome. Am J Med Genet.A 2011;155A:2956-2963. View abstract.
^ The effect of HMB on skeletal muscle damage has been assessed in studies using four different biomarkers of muscle damage or protein breakdown: serum creatine kinase, serum lactate dehydrogenase, urinary urea nitrogen, and urinary 3-methylhistidine. When exercise intensity and volume are sufficient to cause skeletal muscle damage, such as during long-distance running or progressive overload, HMB supplementation has been demonstrated to attenuate the rise in these biomarkers by 20–60%.
However, caffeine does not negate the benefits of creatine loading when not coingested, but just taken before exercise in the same dosage. This result indicates that loading creatine without caffeine on a daily basis, but saving caffeine for select workouts, may be an effective strategy, as creatine does not adversely affect caffeine’s ergogenic effects and may enhance creatine’s effectiveness in anaerobic exertion if the two compounds are alternated.
Eat healthy fats. That's right—not only does it make food taste good, fat is good for you, as long as you are eating the right kinds and amounts of fat! Saturated fats—the fat you'll find in a stick of butter, a bag of chips, or bacon—should be limited to about 20g or less. That's the bad news. The good news is that unsaturated fats are actually beneficial, even necessary. Fat is necessary for the proper distribution of vitamins A, D, E, and K, helps promote better eyesight, and healthy skin. Fats are also important for the synthesis of hormones, so maintaining an adequate intake of them will speed up muscle-building and recovery.
Researchers described the study as one of the first to examine how strength training can reduce the risk of cardiovascular disease, separate from the effects of aerobic activity like running or long walks. The point: for those who are not meeting recommended guidelines for aerobic activity—perhaps because they lack the time—bursts of weight training can be enough.
Most causes of brain injury (calcium influx, excitotoxicity, lipid peroxidation, reactive oxygen intermediates or ROIs) all tend to ultimately work secondary to damaging the mitochondrial membrane and reducing its potential, which ultimately causes cellular apoptosis. Traumatic brain injuries are thought to work vicariously through ROIs by depleting ATP concentrations. Creatine appears to preserve mitochondrial membrane permeability in response to traumatic brain injury (1% of the rat’s diet for four weeks), which is a mechanism commonly attributed to its ATP-buffering ability.
Creatine is thought to improve strength, increase lean muscle mass, and help the muscles recover more quickly during exercise. This muscular boost may help athletes achieve bursts of speed and energy, especially during short bouts of high-intensity activities such as weight lifting or sprinting. However, scientific research on creatine has been mixed. Although some studies have found that it does help improve performance during short periods of athletic activity, there is no evidence that creatine helps with endurance sports. Research also shows that not everyone's muscles respond to creatine; some people who use it see no benefit.
In isolated striatal cells (expressing creatine kinase), seven day incubation of 5mM creatine (maximal effective dose) appears to increase the density of GABAergic neurons and DARPP-32 (biomarker for spiny neurons) with only a minor overall trend for all cells and showed increased GABA uptake into these cells, as well as providing protection against oxygen and glucose deprivation.
How much weight? Start with a pair of light dumbbell hand weights (2 to 3 pounds for women and 5 to 8 pounds for men). If you can’t do 12 repetitions (or reps are the number of times you do the exercise) the weight is too heavy. If your muscles don’t feel tired after 12 reps, it’s too light. Adjustable weights that can be strapped to wrists or ankles may be convenient if you have arthritis in your hands. You can also use home or gym weight machines, or resistance bands.
As mentioned earlier, supplementation of creatine in youth has been noted to improve the swim bench test (a thirty second sprint followed by another after a five minute break). One study noted improvement when examining a 400 meter test after 10g of creatine was taken over seven days with some orange juice. The improvement was mostly attributable to increased performance on the last 50m stretch.
Using too much weight, too soon; always start lower than your expected ability and work your way up that first workout. If your form suffers, you are swinging the weight, or using momentum, this indicates you may be using too much weight. Greater momentum increases the potential for injury and reduces the effectiveness to the muscle group being targeted.
It is suggested [16,37] that another mechanism for the effect of creatine could be enhanced muscle glycogen accumulation and GLUT4 expression, when creatine supplementation is combined with a glycogen depleting exercise. Whereas it has been observed  that creatine supplementation alone does not enhance muscle glycogen storage. Hickner et al  observed positive effects of creatine supplementation for enhancing initial and maintaining a higher level of muscle glycogen during 2 hours of cycling. In general, it is accepted that glycogen depleting exercises, such as high intensity or long duration exercise should combine high carbohydrate diets with creatine supplementation to achieve heightened muscle glycogen stores .
The body's pool of creatine can be replenished either from food (or supplements) or through synthesis from precursor amino acids. Dietary sources include beef, tuna, cod, salmon, herring, and pork . The normal dietary intake of creatine is 1-2 g/day, although vegetarians may consume less [3,4]. Dietary creatine is absorbed from the intestines into the bloodstream. If the dietary supply is limited, creatine can be synthesized from the body stores of the amino acids glycine, arginine, and methionine. The kidneys use glycine and arginine to make guanidinoacetate, which the liver methylates to form creatine , which is transported to the muscle cells for storage. It is also stored in the kidneys, sperm cells, and brain tissue .
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