Vegetarians and other people who have lower total creatine levels when they start taking creatine supplements seem to get more benefit than people who start with a higher level of creatine. Skeletal muscle will only hold a certain amount of creatine; adding more won't raise levels any more. This "saturation point" is usually reached within the first few days of taking a "loading dose."
Anti-cancer effects have been observed with the creatine analogue cyclocreatine[456][104][457] and have been replicated with creatine itself. These effects tend to be a reduction in which the rate of implanted tumors progresses.[458][459] It is suspected that these observed effects (inhibition of growth or attenuation of the rate of growth) are not due to the bioenergetic effect of creatine, secondary to creatine kinase. These anti-cancer effects do not have a known reliability, as the expression of creatine kinase varies widely based on the type of tumor.[460] However, some studies suggest an inverse relationship between tumor progression in mice and concentrations of creatine in cells, with creatine depletion coinciding with tumor development.[460]
A typical creatine supplementation protocol of either a loading phase of 20 to 25 g CM/d or 0.3 g CM/kg/d split into 4 to 5 daily intakes of 5 g each have been recommended to quickly saturate creatine stores in the skeletal muscle. However a more moderate protocol where several smaller doses of creatine are ingested along the day (20 intakes of 1 g every 30 min) could be a better approach to get a maximal saturation of the intramuscular creatine store. In order to keep the maximal saturation of body creatine, the loading phase must be followed by a maintenance period of 3-5 g CM/d or 0.03 g CM/kg/d. These strategies appear to be the most efficient way of saturating the muscles and benefitting from CM supplementation. However more recent research has shown CM supplementation at doses of 0.1 g/kg body weight combined with resistance training improves training adaptations at a cellular and sub-cellular level. Creatine retention by the body from supplementation appears to be promoted by about 25% from the simultaneous ingestion of carbohydrate and/or protein mediated through an increase in insulin secretion. This combination would produce a faster saturation rate but has not been shown to have a greater effect on performance.
You’ll Feel Better: Not only will you find yourself with more energy and confidence, less stress and anxiety, and a better overall mood, but you’ll actually begin to think better (resistance training has been proven to help increase cognitive function). And while training too close to bedtime can be a bad idea, exercising earlier in the day has been proven to help prevent sleep apnea and insomnia. I even improved my posture – when I started lifting, I was 5’4”.  Now I’m 5’5.5”.
A: Start with the calculations above but don’t be afraid to adjust up or down. Your metabolism and physiology will adapt to more food by trying to maintain homeostasis and regulate your bodyweight. Some may have to increase more than others but the number on the scale doesn’t lie. If it’s not going up, then you probably need to increase your calories.
Note that this recommendation is for total weekly volume, which means it would need to be divided up based on how many times you’re training each muscle group per week. So, for example, someone training everything twice per week would do 30-70 reps for each bigger muscle group in each of those workouts, and 15-35 reps for each smaller muscle group in each of those workouts.
A: If your goal is the largest accrual of muscle mass possible then there may be some benefit to ingesting nutrients with a period of 30-60 minutes after your workout. Does this have to be a protein shake? No, but ideally it should be a meal lower in fat to enhance the digest rate of nutrients within the gastrointestinal tract. However, if you have just eaten a mixed macronutrient meal pre-workout then you should keep in mind that that meal is still likely digesting so there’s no need to throw down the weights after your last set and rush to your locker to slam a protein shake.
Women who train hard and reach low body fat levels, say under 10 percent, may be at risk of losing their periods as a result of hormonal disruption to estrogen production. Exercise-induced estrogen declines can result in bone loss in a way similar to that which occurs at the menopause. Loss of periods from athletic training is not uncommon but does require that you see a doctor, or better still, a sports physician and sports nutritionist to assess what is required to address the problem. Calcium supplements may be a part of the solution if bone health is likely to be affected. 
Kidney damage (from anything) will cause high levels of creatinine in blood, and creatine can also increase blood creatinine levels in a manner that is not due to damaging the kidneys. This results in a false positive when trying to diagnose kidney damange when the subject also supplements creatine, and does not signify any actual damage to the kidneys.
One pilot study using 150mg/kg creatine monohydrate for a five day loading phase followed by maintenance (60mg/kg) for the remainder of the five weeks noted that supplementation was associated with fewer muscle symptoms and complaints alongside improved muscular function,[572] yet a later trial trying to replicate the obsevations using 150mg/kg daily for five weeks noted the opposite, that creatine supplementation exacerbated symptoms.[573]  

“Reg Park’s theory was that first you have to build the mass and then chisel it down to get the quality; you work on your body the way a sculptor would work on a piece of clay or wood or steel. You rough it out””the more carefully, the more thoroughly, the better”” then you start to cut and define. You work it down gradually until it’s ready to be rubbed and polished. And that’s when you really know about the foundation. Then all the faults of poor early training stand out as hopeless, almost irreparable flaws. [..]
In addition to being potentially harmful, some have argued that there is little evidence to indicate any benefit to using bodybuilding protein or amino acid supplements. "In view of the lack of compelling evidence to the contrary, no additional dietary protein is suggested for healthy adults undertaking resistance or endurance exercise".[18] In dispute of this, one more recent meta-analysis concluded that for athletes participating in resistance exercise training and consuming protein supplements for an average of 13 weeks, total protein intake up to 1.6 g per kg body weight per day would result in an increase in strength and fat-free mass, i.e. muscle, but that higher intakes would not further contribute. The muscle mass increase was statistically significant but modest - averaging 0.3 for all trials and 1.0 to 2.0 kg, for protein intake ≥ 1.6 g/kg/day.[3]
In 1912, Harvard University researchers Otto Folin and Willey Glover Denis found evidence that ingesting creatine can dramatically boost the creatine content of the muscle.[5][non-primary source needed] In the late 1920s, after finding that the intramuscular stores of creatine can be increased by ingesting creatine in larger than normal amounts, scientists discovered creatine phosphate, and determined that creatine is a key player in the metabolism of skeletal muscle. The substance creatine is naturally formed in vertebrates.[6]

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Although creatine supplementation has been shown to be more effective on predominantly anaerobic intermittent exercise, there is some evidence of its positive effects on endurance activities. Branch [28] highlights that endurance activities lasting more than 150s rely on oxidative phosphorylation as primary energy system supplier. From this meta analysis [28], it would appear that the ergogenic potential for creatine supplementation on predominantly aerobic endurance exercise diminishes as the duration of the activity increases over 150s. However it is suggested that creatine supplementation may cause a change in substrate utilization during aerobic activity possibly leading to an increase in steady state endurance performance.

The creatine transporter is a sodium[139][140] and chloride[141][142] dependent membrane-associated transporter that belongs to the Na+/Cl-dependent family of neurotransmitter transporters.[143] In muscle cells and most other cell types,[131][141] the isomer of the creatine transporter is known as SLC6A8 (solute carrier family 6, member 8). SLC6A8 is encoded by the gene present on the Xq28 region of the human X-chromosome and is expressed in most tissues.[144] A related gene encoding a creatine transporter variant has also been identified at 16p11.1 that is expressed exclusively in the testes.[145] These two transporters share 98% homology.[144][145]
If you have been training properly for at least three years, you’ll find that advanced pump-enhancing techniques like rest-pause sets, drop sets, and some of the other old-school bodybuilding techniques you’ve no doubt heard of can be effective when used sparingly. Just be sure not to overdo the use of them. And never get away from the most important rule: setting PR’s to get stronger.
Prison food isn’t as bad as people think. Prisoners often get three meals a day. Meals need to meet a certain amount of calories. You don’t need that much protein to build muscle, but prisoners can buy protein powder (and also extra food like oatmeal). Prisoners aren’t underfed in most western countries. The diet may not be optimal, but it’s sufficient to build muscle.
When lifting to complete fatigue, it takes an average of two to five minutes for your muscles to rest for the next set. When using lighter weight and more repetitions, it takes between 30 seconds and a minute for your muscles to rest. For beginners, working to fatigue isn't necessary, and starting out too strong can lead to too much post-exercise soreness.
In regard to practical interventions, concurrent glycogen loading has been noted to increase creatine stores by 37-46% regardless of whether the tissue was exercised prior to loading phase.[176] It is important to note, however, that creatine levels in response to the creatine loading protocol were compared in one glycogen-depleted leg to the contralateral control leg, which was not exercised.[176] This does not rule out a possible systemic exercise-driven increase in creatine uptake, and the increase in creatine noted above[176] was larger than typically seen with a loading protocol (usually in the 20-25% range). Consistent with an exercise-effect, others have reported that exercise itself increases creatine uptake into muscle, reporting 68% greater creatine uptake in an exercised limb, relative to 14% without exercise.[153]
^ Spillane M, Schoch R, Cooke M, Harvey T, Greenwood M, Kreider R, Willoughby DS (February 2009). "The effects of creatine ethyl ester supplementation combined with heavy resistance training on body composition, muscle performance, and serum and muscle creatine levels". Journal of the International Society of Sports Nutrition. 6 (1): 6. doi:10.1186/1550-2783-6-6. PMC 2649889. PMID 19228401.
It’s perhaps best known for the aesthetic benefits. Creatine increases muscle size relatively quickly and while that’s in part due to an increase in muscle water content — a good thing, since it means we’re better hydrated — it does indeed appear to lead to actual hypertrophy over time. And bigger muscles aren’t just aesthetic: larger muscles can improve work capacity, explosiveness, fat oxidation, injury resilience, and recovery.
These effects were noted before in a preliminary study of depressed adolescents (with no placebo group) showing a 55% reduction in depressive symptoms at 4g daily when brain phosphocreatine levels increased.[231] Other prelimnary human studies suggest creatine might lessen unipolar depression[256] and one study on Post-Traumatic Stress Disorder (PTSD) noted improved mood as assessed by the Hamilton Depression Rating Scale.[232]
Safety. In general health terms, most medical opinion is that up to three cups of coffee a day are not harmful, and may even have some benefits, although some people respond to the stimulant properties with more problems than others. Heart palpitations and restlessness are experienced by some caffeine drinkers. In pregnancy, one or two cups each day are thought to be without harm to the fetus.

Creatine ethyl ester is more a pronutrient for creatinine rather than creatine,[74] and was originally created in an attempt to bypass the creatine transporter. It is currently being studied for its potential as a treatment for situations in which there is a lack of creatine transporters (alongside cyclocreatine as another possible example).[77] Its efficacy may rely on intravenous administration, however.
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