In females, the combination of SSRIs (to increase serotonin levels in the synapse between neurons) and creatine shows promise in augmenting the anti-depressive effects of SSRI therapy. Another pilot study conducted on depression and females showed efficacy of creatine supplementation. The one study measuring male subjects noted an increase in mood and minimal anti-depressive effects, but it is not know whether this is due to gender differences or the model studies (post-traumatic stress disorder).
Chwalbinska-Monteta  observed a significant decrease in blood lactate accumulation when exercising at lower intensities as well as an increase in lactate threshold in elite male endurance rowers after consuming a short loading (5 days 20 g/d) CM protocol. However, the effects of creatine supplementation on endurance performance have been questioned by some studies. Graef et al  examined the effects of four weeks of creatine citrate supplementation and high-intensity interval training on cardio respiratory fitness. A greater increase of the ventilatory threshold was observed in the creatine group respect to placebo; however, oxygen consumption showed no significant differences between the groups. The total work presented no interaction and no main effect for time for any of the groups. Thompson et al  reported no effects of a 6 week 2 g CM/d in aerobic and anaerobic endurance performance in female swimmers. In addition, of the concern related to the dosage used in these studies, it could be possible that the potential benefits of creatine supplementation on endurance performance were more related to effects of anaerobic threshold localization.
In another case, supplements touted as "myostatin blockers" were formulated from a type of sea algae. In a test tube, they effectively blocked the activity of the protein myostatin, which inhibits muscular growth in the body. The supplement ads implied that they'd enable you to develop unprecedented levels of muscular growth, but as it turned out, they didn't actually work in the human body.
The creatine transporter is a sodium and chloride dependent membrane-associated transporter that belongs to the Na+/Cl-dependent family of neurotransmitter transporters. In muscle cells and most other cell types, the isomer of the creatine transporter is known as SLC6A8 (solute carrier family 6, member 8). SLC6A8 is encoded by the gene present on the Xq28 region of the human X-chromosome and is expressed in most tissues. A related gene encoding a creatine transporter variant has also been identified at 16p11.1 that is expressed exclusively in the testes. These two transporters share 98% homology.
Supplementation of a loading phase of creatine has been noted to augment the increase in RBC levels of superoxide dismutase (SOD) from exercise, when measured immediately after, by 8.1%, but control groups increased to match within an hour. Glutathione (normally decreases with exercise) and catalase (increases) were both unaffected, and elsewhere in vitro red blood cells incubated with 3mM of creatine (within the supplemental range) is able to improve filterability (a measure of cell rheology, or fluid structure of the cell) when RBC creatine was increased by 12.3% to reach 554µM. This was thought to be due to reduced oxidative stress (assessed via MDA) in the red blood cells, which in the presence of 1-5mM creatine was progressively reduced by 20-41%.
I learned from this to focus on the body weight exercises. I never understood why I could lift a lot of weight, but felt weak when it came to dips, pull ups, push ups etc. Normally I spend 2 hours in a gym: 20 min jogging, 80 min lifting, 20 min jogging, 5 days a week. After reading this I’m excited to incorporate HIIT training in addition to mobility training on my off days, because I think I was wasting a lot of time and effort. I can push way harder on lifting days without the jog beforehand, so I’ll also be able to make the most of 60 minutes…
Creatine is an energy substrate: a small peptide serving as a reservoir for high-energy phosphate groups that can regenerate ATP, the main currency of cellular energy. An increase in creatine intake (through food or supplementation) increases cellular energy stores, promoting the regeneration of ATP in the short term. Stores are limited, however, and glucose or fatty acids are responsible for ATP replenishment over longer durations.
However, if you increase the demands you are placing on your body by increasing the weight being lifted, lifting the same weight for additional reps, or just doing something that increases the demands that your body needs to meet, then your body will have no other choice but to make the changes and improvements necessary for it to adapt to this environment and remain capable of performing these tasks.
If you decide to join a gym, know that you're not expected to know how all of the equipment works right off the bat—or what to do with it. Be sure to take advantage of the free orientation so you can learn how to properly use everything that's offered and set up a basic strength-training program. At the gym, machines are preferred for beginners, because they're quite safe: Most require little coordination and offer more stability than free weights while performing the movements.
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).
Young adult athletes who reported creatine usage for over two years prior to the study (retrospective design) were not significantly different than controls. Elsewhere, in a similar cohort of athletes reporting creatine usage for up to four years, failed to note significant differences in liver enzymes, although a nonsignificant reduction in LDH was noted.
That pump is tangible, real-time biofeedback to let you know that blood is flowing to your muscle cells, beginning a chain of events that stimulates protein synthesis. Maybe that's why it's easy to overlook how important good nutrition is in the mass-building equation. When you choose to eat, say, chicken instead of ice cream, there's no immediate muscle gratification -- no pump to keep you motivated.
In your body, you can only store enough ATP for about 10 seconds of maximum exercise, this means that after those storages are depleted, it is up to your body to produce ATP to reach the demand your body is placing.  Creatine helps in the body by increasing stores of phosphocreatine which is the main ingredient used to create new ATP during intense exercise. By just supplementing creatine for 6 days, you can double your levels of creatine in your muscle storages, resulting in a higher capacity to create energy. 
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.
Sports where strength training is central are bodybuilding, weightlifting, powerlifting, and strongman, highland games, hammer throw, shot put, discus throw, and javelin throw. Many other sports use strength training as part of their training regimen, notably: American football, baseball, basketball, football, hockey, lacrosse, mixed martial arts, rowing, rugby league, rugby union, track and field, boxing and wrestling.
A meta-analysis found that creatine treatment increased muscle strength in muscular dystrophies, and potentially improved functional performance. Creatine treatment does not appear to improve muscle strength in people who have metabolic myopathies. High doses of creatine lead to increased muscle pain and an impairment in activities of daily living when taken by people who have McArdle disease.
Spero Karas, MD, assistant professor of orthopaedics in the division of sports medicine at Emory University, says that testosterone, the male hormone responsible for muscle growth, maxes out between the ages of 16 and 18. It reaches a plateau during the 20s and then begins to decline. As a result, muscle building after the adolescent years can be challenging, he says.
Increasing creatine levels in skeletal muscle to 687% of baseline (0.5mM creatine, thought to be equivalent to 5g creatine) doesn’t seem to per se increase glucose uptake, but increases glucose oxidation (140% of baseline) which is due to a two-fold increase in the activity of α1 and α2 subunits of AMPK, a potency comparable to 1mM of the reference drug AICAR. Glucose uptake associated with AMPK has indeed been noted in diabetic people who are undergoing physical exercise and in contracting skeletal muscle cells, but according to rat and in vitro studies of cells not being contracted, this is not a per se effect of non-exercising tissue but an augmentation of exercise-induced glucose uptake.
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.