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).
In a mouse model of allergin-induced asthma, where mice were sensitized by ovalbumin for three weeks and then given 500mg/kg creatine, supplementation induced an increase in asthmatic hyperresponsiveness to low but not high doses of methacholine. This hyperresponsiveness was associated with increased eosinophil and neutrophil infiltration into the lungs, and an increase in Th2 cell cytokines (IL-4 and IL-5) alongside an increase in IGF-1, which is known to influence this process. Interestingly, there was a nonsignificant increase in responsiveness in mice not sensitized to ovalbumin.
Exercise is highly effective in increasing your lean body mass, which is essentially muscle. In a study published in 2012, progressive resistance training helped men ages 50 to 83 gain an average of 2.4 pounds of lean body mass over an average of 20.5 weeks. Progressive resistance training involves performing weight bearing exercises. In addition, you must slowly increase the challenge of the exercise over time by increasing the weight, reps and/or sets. Studies show that either increasing reps or weight amount will work. So, if you don’t want to lift more weight, you can just do more reps and still build muscle.
It is known that intracellular energy depletion (assessed by a depletion of ATP) stimulates AMPK activity in order to normalize the AMP:ATP ratio, and when activated AMPK (active in states of low cellular energy and colocalizes with creatine kinase in muscle tissue) appears to inhibit creatine kinase via phosphorylation (preserving phosphocreatine stores but attenuating the rate that creatine buffers ATP). While phosphocreatine technically inhibits AMPK, this does not occur in the presence of creatine at a 2:1 ratio. It seems that if the ratio of phosphocreatine:creatine increases (indicative of excess cellular energy status) that AMPK activity is then attenuated, since when a cell is in a high energy status, there is less AMP to directly activate AMPK.