In vitro studies on endothelial cells have noted that the benefits of creatine against atherosclerosis (via immune cell adhesion to the endothelial cell) are blocked with the pharmaceutical ZM241385, a high affintiy adenosine A2A receptor antagonist.[316] This particular receptor subset (A2A rather than other adenosine receptors) and its inhibition are similar to caffeine,[589] suggesting that caffeine may have an inhibitory effect on this mechanism of creatine.
^ Haykowsky MJ, Liang Y, Pechter D, Jones LW, McAlister FA, Clark AM (June 2007). "A meta-analysis of the effect of exercise training on left ventricular remodeling in heart failure patients: the benefit depends on the type of training performed". Journal of the American College of Cardiology. 49 (24): 2329–36. doi:10.1016/j.jacc.2007.02.055. PMID 17572248.

Glutamine and beta-alanine are amino acids and HMB, beta-hydroxy-beta-methyl butyrate, is a byproduct of leucine, another amino acid. Promoting individual amino acids, the building blocks of protein, to enhance performance in the strength sports has been a particular focus of supplement manufacturers over the years. To date, the evidence for any advantage has been mixed and mostly unimpressive.
Creatine is not an essential nutrient[19] as it is naturally produced in the human body from the amino acids glycine and arginine, with an additional requirement for methionine to catalyze the transformation of guanidinoacetate to creatine. In the first step of the biosynthesis these two amino acids are combined by the enzyme arginine:glycine amidinotransferase (AGAT, EC:2.1.4.1) to form guanidinoacetate, which is then methylated by guanidinoacetate N-methyltransferase (GAMT, EC:2.1.1.2), using S-adenosyl methionine as the methyl donor. Creatine itself can be phosphorylated by creatine kinase to form phosphocreatine, which is used as an energy buffer in skeletal muscles and the brain.
Chwalbinska-Monteta [34] observed a significant decrease in blood lactate accumulation when exercising at lower intensities as well as an increase in lactate threshold in elite male endurance rowers after consuming a short loading (5 days 20 g/d) CM protocol. However, the effects of creatine supplementation on endurance performance have been questioned by some studies. Graef et al [35] examined the effects of four weeks of creatine citrate supplementation and high-intensity interval training on cardio respiratory fitness. A greater increase of the ventilatory threshold was observed in the creatine group respect to placebo; however, oxygen consumption showed no significant differences between the groups. The total work presented no interaction and no main effect for time for any of the groups. Thompson et al [36] reported no effects of a 6 week 2 g CM/d in aerobic and anaerobic endurance performance in female swimmers. In addition, of the concern related to the dosage used in these studies, it could be possible that the potential benefits of creatine supplementation on endurance performance were more related to effects of anaerobic threshold localization. 

Competitive and professional bodybuilders, however, can often build up to two to three pounds of muscle per month during dedicated bulking periods. "But they are living and breathing muscle growth. They aren't just in and out of the gym like most people," Simpson says, noting that under extreme conditions, hyperplasia, or the growth in the number of muscle cells in a given muscle tissue, may actually occur, further adding to muscle growth results.
On top of this, you’ll need to consume more calories than you’re burning. Burning more calories each day than you eat is a great way to lose weight, but if your goal is to put on muscle mass, this can make the process much harder. Your body requires calories to build new muscle tissue, but this can’t occur if all the body’s energy is being used up for daily processes. Because of this, some bodybuilding supplements include weight gainers to help you get more healthy calories in your diet.
Creatine has been investigated for its effects on depression, due to the significant changes occurring in brain morphology and neuronal structure associated with depression[246] and low brain bioenergetic turnover in depression[247], perhaps related to abnormal mitochondrial functioning, which reduces available energy for the brain.[248][249] The general association of low or otherwise impaired phosphate energy systems (of which creatine forms the energetic basis of) with depression, has been noted previously.[250][247][251] Due to associations with cellular death and impaired bioenergetics with depression, creatine was subsequently investigated.
Creatine monohydrate is highly regarded as one of the most powerful and all-around best bodybuilding supplements for athletes hoping to make big gains fast. Creatine is one of the go-to supplements for building mass because it maximizes power output, strength, endurance, and overall performance, helping you to crush your fitness goals time and time again.

A: Depending upon your experience level, preference, recovery capacity, and time available, you’ll likely find that 3-5 strength training sessions per week is the sweet spot. If you’re just getting started with weight training, then you should stick with 3 days per week and work your way up. Novices and early intermediates can handle 4 days per week with a split such as an upper lower and seasoned intermediate lifters may be able to handle 5 sessions per week depending upon the programming, recovery, and nutrition strategies that are in place.
If there are any benefits for swimming performance from creatine supplementation, they appear to be limited to a 50 meter sprint or a handful of 50 meter sprints with short intermissions. Excessive sprinting (over six sprints with short breaks) or too long of a break (five minutes rather than two) seem to not be associated with the benefits of creatine supplementation.
Of the three, protein will of course play the most important role in the muscle building process (like calories, it’s one our required “supplies”), although fat and carbs will still be important for other reasons which range from optimizing hormone production (e.g. testosterone, the muscle building hormone) to enhancing training performance and recovery.
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]
Creatine synthesis primarily occurs in the liver and kidneys.[2][16] On average, it is produced endogenously at an estimated rate of about 8.3 mmol or 1 gram per day in young adults.[16][17] Creatine is also obtained through the diet at a rate of about 1 gram per day from an omnivorous diet.[16][18] Most of the human body's total creatine and phosphocreatine stores are found in skeletal muscle, while the remainder is distributed in the blood, brain, and other tissues.[17][18]
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Researchers found that 5g of creatine four times daily for a week (loading) before sleep deprivation for 12-36 hours was able to preserve cognition during complex tasks of executive function at 36 hours only, without significant influence on immediate recall or mood.[279] A similar protocol replicated the failure to improve memory and attention, but noted less reports of fatigue (24 hours) and less decline of vigor (24 hours) although other mood parameters were not measured.[276]
While this nonessential amino acid may not deliver earth-shattering PRs or extreme muscle growth, it does play an important role in repair and recovery. Glutamine works by removing excess ammonia, which can accumulate during intense exercise, helping to regulate your body's acid-base balance. Individuals who are engaged in heavy resistance training, two-a-day training splits, or are in a calorie deficit may benefit from the extra support of glutamine supplementation.
Creatine kinase enzymes (of which there are numerous isozymes) exist in both the mitochondria and the cytosol of the cell.[45][40] The four isozymes of creatine kinase include the Muscle Creatine Kinase (MCK), present in contractile muscle and cardiac muscle, and the Brain Creatine Kinase (BCK), expressed in neuron and glial cells and several other non-muscle cells. These two creatine kinases are met with Sarcolemmic Mitochondrial Creatine Kinase (sMitCK), expressed alongside MCK, and the ubiquitous Mitochondrial Creatine Kinase (uMitCK), which is expressed alongside BCK everywhere else.[25][39]
These complete proteins include all of the essential amino acids that the body cannot produce itself. Different proteins, such as whey and casein, egg and soy have different absorption rates. Whether you should favor one over another for muscle building is still a subject of popular and scientific debate, although whey protein isolate, a more rapidly absorbed protein, has some support from various scientific studies. For protein powders, assess the value by checking out the protein listed on the label. Combined with resistance training, sufficient protein consumption along with an appropriate diet can lead to increased muscle and reduced body fat. You should read more about The Bodybuilding Diet for supplement timing issues before and after training. 
Creatine is most commonly found in the basic form of creatine monohydrate, which is the standard form and usually recommended due to the low price. It can also be micronized to improve water solubility, or the monohydrate can be temporarily removed to concentrate creatine in a small volume supplement. Neither alteration changes the properties of creatine.

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]
On top of this, you’ll need to consume more calories than you’re burning. Burning more calories each day than you eat is a great way to lose weight, but if your goal is to put on muscle mass, this can make the process much harder. Your body requires calories to build new muscle tissue, but this can’t occur if all the body’s energy is being used up for daily processes. Because of this, some bodybuilding supplements include weight gainers to help you get more healthy calories in your diet.
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