In people whose kidneys don’t function optimally, supplemental creatine seems to be safe, too.[513][518][313][528] However, studies in people with suboptimal kidney function are fewer than in healthy people, and they are short-term. People with kidney dysfunction, or at risk for developing kidney dysfunction (e.g., people with diabetes, high blood pressure, or family history of kidney disease; people over sixty; and non-Hispanic blacks), might wish to forgo creatine, or otherwise take only the lowest effective dose (3 g/day)[527] after talking to their doctor.
Creatine supplementation appears to attenuate decreases in GLUT4 expression seen with immobility and may increase GLUT4 expression during exercise. While it seems capable of increasing GLUT4 during resting conditions, it has failed to reach significance, suggesting that creatine supplementation works best with some stimuli associated with exercise.
Another category of muscle-building supplements that lifters and bodybuilders use to improve their results are branched-chained amino acids (BCAAs), or BCAAs. Of the 20 amino acids that make up protein, just three are referred to as BCAAs: leucine, isoleucine, and valine. These are the specific amino acids that have been shown to stimulate protein synthesis and help regulate protein metabolism.
Escolar, D. M., Buyse, G., Henricson, E., Leshner, R., Florence, J., Mayhew, J., Tesi-Rocha, C., Gorni, K., Pasquali, L., Patel, K. M., McCarter, R., Huang, J., Mayhew, T., Bertorini, T., Carlo, J., Connolly, A. M., Clemens, P. R., Goemans, N., Iannaccone, S. T., Igarashi, M., Nevo, Y., Pestronk, A., Subramony, S. H., Vedanarayanan, V. V., and Wessel, H. CINRG randomized controlled trial of creatine and glutamine in Duchenne muscular dystrophy. Ann Neurol 2005;58:151-155. View abstract.
Prohormones are precursors to hormones and are most typically sold to bodybuilders as a precursor to the natural hormone testosterone. This conversion requires naturally occurring enzymes in the body. Side effects are not uncommon, as prohormones can also convert further into DHT and estrogen. To deal with this, many supplements also have aromatase inhibitors and DHT blockers such as chrysin and 4-androstene-3,6,17-trione. To date most prohormone products have not been thoroughly studied, and the health effects of prolonged use are unknown. Although initially available over the counter, their purchase was made illegal without a prescription in the US in 2004, and they hold similar status in many other countries. They remain legal, however, in the United Kingdom and the wider European Union. Their use is prohibited by most sporting bodies.
Fast twitch (or Type II fibers) fire very quickly, but also fatigue quickly, so they don’t last long.  It gets a bit more complicated, because there are actually two types of fast twitch fibers. Type IIA fibers have some endurance qualities (used for things such as longer sprints). While Type IIX fibers are our “super fast” fibers, used only when a super short burst is needed (like a 100 m sprint or a really heavy lift).
SAMe is the primary methyl donor in the human body, and supplements that preserve SAMe (such as trimethylglycine; TMG) promote a variety of benefits in the human body, like a reduction in homocysteine and reduced risk of fatty liver. Creatine has been implicated in both reducing homocysteine[124] and preventing fatty liver in rodents[125], thought to be secondary to preserving SAMe.
There appears to be some potential for creatine supplementation. However, many questions remain. Are there any long-term harmful effects from supplementation? Is there a point where enhanced performance levels off from long-term supplement usage? What effect does "stacking" or taking two ergogenic aids simultaneously have on the body? What happens if you immediately stop taking the creatine supplement? Is the enhanced performance great enough to warrant the expense of the supplement? Until further research answers these questions, creatine is not recommended for the average athlete.
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In well-trained endurance runners, creatine (with glycerol for hyperhydration) caused a relatively large increase in body weight gain (0.90+/-0.40kg) and water weight (0.71+/-0.42L) but failed to negatively influence performance over 30 minutes in the heat.[3] This failure to improve physical performance in the heat with creatine loading (despite water retention) has been noted elsewhere.[346]

In elite swimmers, the growth hormone response to sprints appears to be attenuated (39%) following creatine loading, although after a 3g maintenance phase (22-27 weeks), this attenuation was reduced to less than 5%.[404] Elsewhere in swimmers, resting growth hormone was unaffected by the loading phase,[397] suggesting that this is an exercise-exclusive effect.
Stronger muscles improve performance in a variety of sports. Sport-specific training routines are used by many competitors. These often specify that the speed of muscle contraction during weight training should be the same as that of the particular sport. Sport-specific training routines also often include variations to both free weight and machine movements that may not be common for traditional weightlifting.
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.
Other supplements could easily have been included here, but these are considered the most useful and effective for the majority of bodybuilders and athletes. Although food should always come first, supplements offer an effective alternative for getting nutrients that either aren't available in sufficient quantity in food or are in foods that you may not be eating.
There is a great amount of research published on creatine supplementation; protocols of administration, forms of creatine, as well as potential side effects. Despite this, the mechanisms by which creatine acts in the human body to improve physical and cognitive performance are still not clear. The main objectives of this review are to analyze the more recent findings on the effects and mechanisms of creatine supplementation in sports and health. As a secondary purpose, we will analyze the most recommended protocols of ingestion and its potential side effects.
The bulking and cutting strategy is effective because there is a well-established link between muscle hypertrophy and being in a state of positive energy balance.[19] A sustained period of caloric surplus will allow the athlete to gain more fat-free mass than they could otherwise gain under eucaloric conditions. Some gain in fat mass is expected, which athletes seek to oxidize in a cutting period while maintaining as much lean mass as possible.

Studies of so-called "smart drugs" have also been taken out of context. Some "smart" nutrients, available over the counter, are marketed as a way to "increase mental focus and concentration during training." The problem is that the studies they're based upon involved either animals or people with brain pathology. In normal people the effects of smart drugs remain unproven, except anecdotally.


In regard to the blood brain barrier (BBB), which is a tightly woven mesh of non-fenestrated microcapillary endothelial cells (MCECs) that prevents passive diffusion of many water-soluble or large compounds into the brain, creatine can be taken into the brain via the SLC6A8 transporter.[192] In contrast, the creatine precursor (guanidinoacetate, or GAA) only appears to enter this transporter during creatine deficiency.[192] More creatine is taken up than effluxed, and more GAA is effluxed rather than taken up, suggesting that creatine utilization in the brain from blood-borne sources[192] is the major source of neural creatine.[193][192] However, “capable of passage” differs from “unregulated passage” and creatine appears to have tightly regulated entry into the brain in vivo[193]. After injecting rats with a large dose of creatine, creatine levels increased and plateaued at 70uM above baseline levels. These baseline levels are about 10mM, so this equates to an 0.7% increase when superloaded.[193] These kinetics may be a reason for the relative lack of neural effects of creatine supplementation in creatine sufficient populations.
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