When looking specifically at human studies, there has been a failure of creatine supplementation to induce or exacerbate kidney damage in people with amyotrophic lateral sclerosis (ALS). Subjects do not experience kidney damage for up to or over a year’s worth of supplementation in the 5-10g range. Postmenopausal women, people with type II diabetes, people on hemodialysis, otherwise healthy elderly, young people, and athletes do not experience kidney damage either. Moreover, numerous scientific reviews on both the long- and short-term safety of supplemental creatine have consistently found no adverse effects on kidney function in a wide range of doses. However, while doses >10 g/day have been found not to impair kidney function, there are fewer long-term trials using such high chronic daily intakes.
In a pilot study on youth with cystic fibrosis, supplementation of creatine at 12g for a week and 6g for eleven weeks afterward was associated with a time-dependent increase in maximal isometric strength reaching 14.3%, which was maintained after 12-24 weeks of supplement cessation (18.2% higher than baseline). This study noted that more patients reported an increase in wellbeing (9 subjects, 50%) rather than a decrease (3, 17%) or nothing (6, 33%) and that there was no influence on chest or lung symptoms.
There is a nuclear receptor known as TIS1 (orphan receptor, since there are no known endogeouns targets at this time) which positively influences transcription of new creatine transporters and, in C2C12 myotubes, seems to be responsive to cAMP or adenyl cyclase stimulation from forskolin (from Coleus Forskohlii) with peak activation at 20µM.
Reducing creatine synthesis by supplementing it has preliminary evidence supporting its ability to reduce homocysteine concentrations in the body, since the synthesis of creatine would normally produce some homocysteine as a byproduct. This may apply to a certain subset of people (MTHFR TT homozygotes, about 10% of North Americans) but at the moment there is not enough evidence to suggest that this occurs in all people supplementing creatine.
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.
Kilduff, L. P., Georgiades, E., James, N., Minnion, R. H., Mitchell, M., Kingsmore, D., Hadjicharlambous, M., and Pitsiladis, Y. P. The effects of creatine supplementation on cardiovascular, metabolic, and thermoregulatory responses during exercise in the heat in endurance-trained humans. Int J Sport Nutr Exerc Metab 2004;14(4):443-460. View abstract.
It may seem odd to put such a common supplement as minerals on this list, but few people are aware that minerals are enzyme activators. Many vitamins, on the other hand, are coenzymes, which means that without minerals they're useless. Many minerals, such as zinc and chromium, also interact with various anabolic hormones, such as testosterone, growth hormone and insulin.
Osteoblast cells are known to express creatine kinase. Bone growth factors such as IGF-1, PTH, and even Vitamin D seem to induce bone growth alongside increases in creatine kinase activity. Vitamin D has been noted to work indirectly by increasing the cellular energy state (these hormones increase creatine kinase in order to do so) in order to make bone cells more responsive to estrogen. This evidence, paired with enhanced growth rates of osteoblasts in the presence of higher than normal (10-20mM) concentrations of creatine suggest a role of creatine in promoting osteoblastic and bone growth, secondary to increasing energy availability.