This cellular influx may also decrease protein oxidation rates, which leads to increases in nitrogen balance and indirectly increases muscle mass.[379] This lowering of protein oxidation is from signaling changes caused vicariously through cell swelling[380][381] and appears to upregulate 216 genes[378] in a range of 1.3 to 5-fold increases, with the largest increase seen in the protein involved in satellite cell recruitment, sphingosine kinase-1. Most importantly for muscle hypertrophy, the protein content of PKBa/Akt1, p38 MAPK, and ERK6 increased 2.8+/-1.2 fold.[378] Sixty-nine genes are also downregulated after creatine supplementation, to less notable degrees.
A loading phase of 10g creatine monohydrate for two weeks and 4g for the final week in subjects with MELAS (Mitochondrial Encephalomyopathy Lactic Acidosis and Stroke-like episodes) has been noted to increase physical strength relative to baseline, although the poor VO2 max seen in these subjects was not affected.[549] A case study exists in which a patient with a relatively novel mutation in their mitochondrial function (affecting cytochrome B) experienced benefits from creatine at 10g daily.[550] Researchers examining another case of MELAS found both cognitive and physical benefits with 5g creatine supplementation,[551] while four controlled case studies of 100-200mg/kg daily in children with myopathies found improved muscular endurance (30-57%) and muscular power (8-17%) after 100-200mg/kg daily for at least three months.[552]
In October 1994, the Dietary Supplement Health and Education Act (DSHEA) was signed into law in the USA. Under DSHEA, responsibility for determining the safety of the dietary supplements changed from government to the manufacturer and supplements no longer required approval from the U.S. Food and Drug Administration (FDA) before distributing product. Since that time manufacturers did not have to provide FDA with the evidence to substantiate safety or effectiveness unless a new dietary ingredient was added. It is widely believed that the 1994 DSHEA further consolidated the position of the supplement industry and lead to additional product sales.[6]
Creatine is old school and definitely hit a pop culture zenith, but that doesn’t make it out-dated or irrelevant today. Creatine supplementation gets results. For starters, one study from Medicine and Science in Sports and Exercise confirms that creatine supplementation can enhance physical performance, claiming that it “exhibits small but significant physiological and performance changes.”

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Despite creatine not interfering with UV(A) irradiation acting upon a cell or the production of oxidation due to it, creatine appears to prevent the functional consequences (such as mitochondrial DNA damage) due to preventing an ATP depletion in the cell, which would normally precede a reduction in mitochondrial membrane potential and mutagenesis, but this effect is prevented for as long as creatine stores are sufficient.[446] Creatine has also been noted to near-fully protect mitochondrial DNA from hydroxyl radicals and oxidative damage, although there was no protective effect for nuclear DNA, due to it being less sensitive to hydroxyl radicals.[447]
Creatine is an organic acid naturally occurring in the body that supplies energy to muscle cells for short bursts of energy (as required in lifting weights) via creatine phosphate replenishment of ATP. A number of scientific studies have shown that creatine can improve strength,[32] energy,[33] muscle mass, and recovery times. In addition, recent studies have also shown that creatine improves brain function.[34] and reduces mental fatigue.[35] Unlike steroids or other performance-enhancing drugs, creatine can be found naturally in many common foods such as herring, tuna, salmon, and beef.
Do a single set of repetitions. Theories on the best way to approach weight training abound, including countless repetitions and hours at the gym. But research shows that a single set of exercise with a weight that fatigues your muscle after about 12 to 15 repetitions can build muscle efficiently in most people and can be as effective as three sets of the same exercise.
Related to exercise and fitness, BCAAs are taken to help reduce muscle breakdown, which is why they may be known as muscle building supplements. Leucine, in particular, is known for playing an important role in muscle protein synthesis, which can help with muscle gain and maintenance. Some also claim that BCAAs can enhance performance, although many studies also refute this claim.
Taking high doses of creatine might harm the kidneys. Some medications can also harm the kidneys. Taking creatine with medications that can harm the kidneys might increase the chance of kidney damage.

Some of these medications that can harm the kidneys include cyclosporine (Neoral, Sandimmune); aminoglycosides including amikacin (Amikin), gentamicin (Garamycin, Gentak, others), and tobramycin (Nebcin, others); nonsteroidal anti-inflammatory drugs (NSAIDs) including ibuprofen (Advil, Motrin, Nuprin, others), indomethacin (Indocin), naproxen (Aleve, Anaprox, Naprelan, Naprosyn), piroxicam (Feldene); and numerous others.

One study in elite swimmers subject to sprints (varying in length from 25-100m) failed to find benefit with creatine supplementation, although there was also a failure on leg extension strength, suggesting nonresponse.[399] This has been noted twice elsewhere with a similar protocol,[400][401] while one study in elite swimmers subject to single 50m or 100m sprints found benefit with supplementation[402] and one found benefit with six repeated 50m sprints by 2%, yet not ten repeated 25m sprints with elite male swimmers (females failed to find benefit).[403] Another study also noted benefits in elite swimmers on a sprinting protocol.[156] Overall, the evidence is quite limited and suggests either a mild, or more likely, no increase for elite swimmers, although one study confirming an increase in body and water weight[401] failed to find a decrement in performance.

Sandow organized the first bodybuilding contest on September 14, 1901, called the "Great Competition". It was held at the Royal Albert Hall in London. Judged by Sandow, Sir Charles Lawes, and Sir Arthur Conan Doyle, the contest was a great success and many bodybuilding enthusiasts were turned away due to the overwhelming amount of audience members.[4] The trophy presented to the winner was a gold statue of Sandow sculpted by Frederick Pomeroy. The winner was William L. Murray of Nottingham. The silver Sandow trophy was presented to second-place winner D. Cooper. The bronze Sandow trophy — now the most famous of all — was presented to third-place winner A.C. Smythe. In 1950, this same bronze trophy was presented to Steve Reeves for winning the inaugural NABBA Mr. Universe contest. It would not resurface again until 1977 when the winner of the IFBB Mr. Olympia contest, Frank Zane, was presented with a replica of the bronze trophy. Since then, Mr. Olympia winners have been consistently awarded a replica of the bronze Sandow.

Those micro-tears that are such a key factor for muscle-building need rest to rebuild themselves and grow stronger. When do they do that? When you’re asleep! “You have to rest and feed your muscles between workouts or you will tear them down and they will become weaker,” says Olson. “Over time, you run the risk of over-training, which can result in injury, and possibly even more sleep troubles.”
Collectively the above investigations indicate that creatine supplementation can be an effective strategy to maintain total creatine pool during a rehabilitation period after injury as well as to attenuate muscle damage induced by a prolonged endurance training session. In addition, it seems that creatine can act as an effective antioxidant agent after more intense resistance training sessions.