Of the three, protein will of course play the most important role in the muscle building process (like calories, it’s one our required “supplies”), although fat and carbs will still be important for other reasons which range from optimizing hormone production (e.g. testosterone, the muscle building hormone) to enhancing training performance and recovery.
Zinc is important to produce the male hormone testosterone and in building the immune system. Magnesium is an essential component of the nervous system and for maintaining heart health. Both have a range of important biochemical function. Zinc and magnesium are often marketed to bodybuilders in combination in a supplement called ZMA. Zinc is in whole grains, seeds, nuts and particularly meat and oysters. After years of research, no evidence exists to show that either mineral offers bodybuilding or athletic performance enhancement in excess of the recommended dietary requirements.
In humans, studies that investigate links between serotonin and creatine supplementation find that 21 trained males, given creatine via 22.8g creatine monohydrate (20g creatine equivalent) with 35g glucose, relative to a placebo of 160g glucose, was found to reduce the perception of fatigue in hot endurance training, possibly secondary to serotonergic modulation, specifically attentuating the increase of serotonin seen with exercise (normally seen to hinder exercise capacity in the heat) while possibly increasing dopaminergic activity (conversely seen to benefit activity in the heat).
Creatine has demonstrated neuromuscular performance enhancing properties on short duration, predominantly anaerobic, intermittent exercises. Bazzucch et al  observed enhanced neuromuscular function of the elbow flexors in both electrically induced and voluntary contractions but not on endurance performance after 4 loading doses of 5 g creatine plus 15 g maltodextrin for 5/d in young, moderately trained men. Creatine supplementation may facilitate the reuptake of Ca2+ into the sacroplasmic reticulum by the action of the Ca2+ adenosine triphosphatase pump, which could enable force to be produced more rapidly through the faster detachment of the actomyosin bridges.
Peirano, R. I., Achterberg, V., Dusing, H. J., Akhiani, M., Koop, U., Jaspers, S., Kruger, A., Schwengler, H., Hamann, T., Wenck, H., Stab, F., Gallinat, S., and Blatt, T. Dermal penetration of creatine from a face-care formulation containing creatine, guarana and glycerol is linked to effective antiwrinkle and antisagging efficacy in male subjects. J.Cosmet.Dermatol. 2011;10(4):273-281. View abstract.
In 1990, professional wrestling promoter Vince McMahon announced that he was forming a new bodybuilding organization named the World Bodybuilding Federation (WBF). McMahon wanted to bring WWF-style showmanship and bigger prize money to the sport of bodybuilding. A number of IFBB stars were recruited but the roster was never very large and featured the same athletes competing; the most notable winner and first WBF champion was Gary Strydom. McMahon formally dissolved the WBF in July 1992. Reasons for this reportedly included lack of income from the pay-per-view broadcasts of the contests, slow sales of the WBF's magazine Bodybuilding Lifestyles (later WBF Magazine), and the expense of paying multiple six-figure contracts while producing two TV shows and a monthly magazine.
The first open label trial on ALS failed to significantly alter lung function as assessed by FEV (when comparing the rate of decline pretreatment relative to treatment). Creatine has elsewhere failed to benefit lung function at 5g daily for months relative to control and failed to significantly attenuate the rate of lung function deterioration over 16 months at 10g daily and 5g daily over nine months.
When combined with an appropriate exercise program, dietary supplementation with β-hydroxy β-methylbutyrate (HMB) has been shown to dose-dependently augment gains in muscle hypertrophy (i.e., the size of a muscle), muscle strength, and lean body mass, reduce exercise-induced skeletal muscle damage,[note 1] and expedite recovery from high-intensity exercise. HMB is believed to produce these effects by increasing muscle protein synthesis and decreasing muscle protein breakdown by various mechanisms, including activation of the mechanistic target of rapamycin (mTOR) and inhibition of the proteasome in skeletal muscles.
Cyclocreatine appears to be passively diffused through membranes and not subject to the creatine transporter, which can be beneficial for cases where creatine transporter function is compromised (creatine non-response and SLG6A8 deficiency). Similar to other forms of creatine, it buffers ATP concentrations, although its efficacy as a supplement in otherwise healthy people is currently unknown.
Creatine citrate is creatine bound to citric acid, or citrate. Creatine citrate does not differ greatly from monohydrate in regard to absorption or kinetics. Note that creatine citrate is more water-soluble than monohydrate, but creatine absorption is generally not limited by solubility. The increased water solubility may play a factor in palatability.
When endothelial cells have a higher creatine concentration, they appear to be mildly less permeable when incubated with 0.5-5mM creatine, while the higher concentration (5mM) is able to fully ablate TNF-α-induced neutrophil adhesion and both E-selectin and ICAM-1 expression. This effect was prevented with ZM241385, an A2A (adenosine) receptor antagonist, and since adenosine released by this receptor is known to be protective of endothelial cells, it is thought that creatine works vicariously through this receptor and adenosine release, thought to be due to releasing ATP (occurs in response to stress) which protects the cell via the A2A signaling system.
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.