Another study demonstrated that females receiving 4 days of high-dose creatine intake (20 g/day) followed by low-dose creatine intake (5 g/day) during 10 weeks of resistance training (3hours/week) increased muscle PCr concentrations by 6%. Also, maximal strength of the muscle groups trained increased by 20-25%, maximal intermittent exercise capacity of the arm flexors increased by 10-25% and fat-free mass increased by 60% .
You're aiming to kick start muscle hypertrophy, the cellular process that spurs growth. Researchers have found that the best way to initiate that process is by performing two or three sets of an exercise for six to 12 repetitions, with about 30 to 60 seconds' rest between sets. You're damaging the muscles with the work — then the protein you've been consuming will help build them back up even bigger.
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 creatine transporter (CrT) is positively regulated by proteins known to be involved in sensing and responding to the cellular energy state, including the mammalian target of rapamycin (mTOR). Upon activation, mTOR stimulates SGK1 and SGK3 to act upon PIKfyve and subsequently PI(3,5)P2 to increase CrT activity. Beyond mTOR, SGK1 also is stimulated by intracellular calcium and a lack of oxygen (ischemia). Because transient ischemia is associated with increased reactive oxygen species (ROS) production after blood flow is restored (reperfusion) it has been hypothesized that muscle contraction may increase creatine uptake through a similar ROS-mediated mechanism.
Without supplementation, creatine is formed primarily in the liver, with minor contributions from the pancreas and kidneys. The two amino acids, glycine and arginine, combine via the enzyme Arginine:Glycine amidinotransferase (AGAT) to form ornithine and guanidoacetate. This is the first of two steps in creatine synthesis, and although rare, any deficiency of this enzyme can result in mild mental retardation and muscular weakness. AGAT is also the primary regulatory step, and an excess of dietary creatine can suppress activity of AGAT to reduce creatine synthesis by reducing AGAT mRNA levels, rather than resulting in competitive inhibition.
Another study found that one week of creatine supplementation at 25 g/day enhanced muscular performance during repeated sets of bench press and jump squat exercise. Creatine supplementation appeared to allow the subjects to complete their workouts at a higher intensity. The researchers concluded that, over time, working at higher intensities may provide a more intense training stimulus and improved muscular adaptations .
Although creatine is a natural component of food, the amount of food required to supersaturate the muscle with PCr may not be feasible. For example, it could require 22 pounds of meat daily . If creatine monohydrate is proven to be a safe and effective ergogenic aid, creatine supplementation may be the simplest way to increasing muscle stores. It may be beneficial to avoid caffeine if taking creatine supplements. One study showed that caffeine diminished strength gains seen with creatine use .
It is regularly reported that creatine supplementation, when combined with heavy resistance training leads to enhanced physical performance, fat free mass, and muscle morphology [18-22]. A 2003 meta analysis  showed individuals ingesting creatine, combined with resistance training, obtain on average +8% and +14% more performance on maximum (1RM) or endurance strength (maximal repetitions at a given percent of 1RM) respectively than the placebo groups. However, contradicting studies have reported no effects of creatine supplementation on strength performance. Jakobi et al  found no effects of a short term creatine loading protocol upon isometric elbow flexion force, muscle activation, and recovery process. However, this study did not clearly state if creatine supplementation was administered concurrent with resistance training. Bemben et al  have shown no additional benefits of creatine alone or combined with whey protein for improving strength and muscle mass after a progressive 14 weeks (3 days per week) resistance training program in older men. These conflicting results can be explained by the possibility that the supplemented groups were formed by a greater amount of non-responders or even because creatine supplementation was administered on the training days only (3 times a week). This strategy has not been adequately tested as effective in middle aged and older men for maintaining post loading elevated creatine stores .
If you stop getting the results you want after several weeks of working out, it's time to mix things up. You need to challenge or "confuse" your muscles often to keep them growing. You can do this by putting a twist on your basic moves. Do a biceps curl with a reverse grip, for example. Or find a bench for the step-up move shown here. Change up your workout at least every 4 to 6 weeks for the best results.
One case study exists of a man with focal segmental glomerulosclerosis who experienced an accelerated rate of GFR decline during supplementation (5g thrice daily for loading, then a 2g maintenance for seven weeks) which was partially reversed upon supplement cessation. This was deemed strong circumstantial evidence, and the brand of supplement was not named. Elsewhere, interstitial nephritis associated with creatine supplementation has been reported in a man, although symptoms arose four weeks after supplementation started with no evidence to support correlation. Some studies involving athletes and various dietary supplements have attempted to draw a correlation with creatine and cases of rhabdomyolysis. Finally, one study in a diabetic person ingesting both metformin and creatine resulting in metabolic acidosis has attempted to place causation on creatine, but it did not establish causation or circumstantial evidence.