However, caffeine does not negate the benefits of creatine loading when not coingested, but just taken before exercise in the same dosage. This result indicates that loading creatine without caffeine on a daily basis, but saving caffeine for select workouts, may be an effective strategy, as creatine does not adversely affect caffeine’s ergogenic effects and may enhance creatine’s effectiveness in anaerobic exertion if the two compounds are alternated.
Arguably the most influential factor, exercise is what instigates muscle growth. When you exercise, especially if you engage in resistance training, it causes trauma to your muscles. This is exactly what you want because it’s this trauma that triggers a response from your body that grows your muscles. To repair the injury or damage to your muscles, special cells called satellite cells arrive. Typically, your muscle fibers thicken and lengthen in this process. (1)
Glycogen synthesis is known to respond directly and positively to cellular swelling. This was demonstrated in an earlier study, during which rat muscle cells were exposed to a hypotonic solution in vitro to induce cell swelling, which increased glycogen synthesis by 75%. In contrast, exposing these same cells to a hypertonic solution hindered glycogen synthesis by 31%. These changes were not due to alterations in glucose uptake, but are blocked by hindering the PI3K/mTOR signaling pathway. It was later noted that stress proteins of the MAPK class (p38 and JNK) as well as heat shock protein 27 (Hsp27) are activated in response to increasing osmolarity. Furthermore, activation of MAPK signaling in skeletal muscle cells is known to induce myocyte differentiation via GSK3β and MEF2 signaling, which can induce muscle cell growth.
If you’re not lifting super-heavy weights, doing high-intensity workouts, or eating a mainly vegan or vegetarian diet, your body probably makes as much creatine as it needs. “Creatine is naturally found in animal-based products,” says Bates, “so your body can make plenty of creatine as long as you have a balanced diet that includes animal-based products.” Protein sources like beef, chicken, pork, and fish help your body produce the creatine it needs — it varies depending on the source, but, in general, a 3-ounce serving of meat will have about 0.4 grams (g) of creatine, Bates says. (6)
Contrary to the sound of the name, glucosamine is not a glucose replacement drink but a naturally occurring compound that has received publicity and wide support as a supplement for the relief of arthritis pain and possible prevention of further joint damage. Glucosamine has been popular with sports people of all types, including weight trainers, particularly for knee arthritis and pain. Glucosamine seems to be safe to use.
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%. Elsewhere in swimmers, resting growth hormone was unaffected by the loading phase, suggesting that this is an exercise-exclusive effect.
Another part of training isn't just doing the exercises, it's resting between the exercises. This comes with experience, but the general rule is, the higher the reps, the shorter the rest. So, if you're doing 15 reps, you might rest about 30 to 60 seconds between exercises. If you're lifting very heavy, say 4 to 6 reps, you may need up to two or more minutes.
A recent review article published in The American Journal of Clinical Nutrition highlighted the benefits of protein supplementation and showed that supplementing with protein during prolonged (greater than 6 weeks) resistance-type training can lead to significantly greater increases in muscle mass and strength when compared to resistance training without a dietary protein intervention.
Rheumatoid arthritis. Early research shows that taking creatine by mouth daily increases lean muscle mass and may improve muscle strength, but does not improve physical functioning in adults with rheumatoid arthritis. In children, taking a specific supplement containing creatine and fatty acids twice daily for 30 days might reduce pain and swelling. But the effects of creatine alone are not clear.
Creatine is a hydrophilic polar molecule that consists of a negatively charged carboxyl group and a positively charged functional group . The hydrophilic nature of creatine limits its bioavailability . In an attempt to increase creatines bioavailability creatine has been esterified to reduce the hydrophilicity; this product is known as creatine ethyl ester. Manufacturers of creatine ethyl ester promote their product as being able to by-pass the creatine transporter due to improved sarcolemmal permeability toward creatine . Spillane et al  analyzed the effects of a 5 days loading protocol (0.30 g/kg lean mass) followed by a 42 days maintenance phase (0.075 g/kg lean mass) of CM or ethyl ester both combined with a resistance training program in 30 novice males with no previous resistance training experience. The results of this study  showed that ethyl ester was not as effective as CM to enhance serum and muscle creatine stores. Furthermore creatine ethyl ester offered no additional benefit for improving body composition, muscle mass, strength, and power. This research did not support the claims of the creatine ethyl ester manufacturers.