Anti-depressive effects have been noted in woman with major depressive disorder when 5g of creatine monohydrate was supplemented daily for 8 weeks in combination with an SSRI. Benefits were seen at week two and were maintained until the end of the 8-week trial.[253] The improvement in depressive symptoms was associated with significantly increased prefrontal cortex levels of N-acetylaspartate, a marker of neuronal integrity,[254] and rich club connections, which refers to the ability of nerons to make connections to one another.[255]
Creatine is most commonly used for improving exercise performance and increasing muscle mass in athletes and older adults. There is some science supporting the use of creatine in improving the athletic performance of young, healthy people during brief high-intensity activity such as sprinting. Because of this, creatine is often used as a dietary supplement to improve muscle strength and athletic performance. In the U.S., a majority of sports nutrition supplements, which total $2.7 billion in annual sales, contain creatine.
Prohormones are precursors to hormones and are most typically sold to bodybuilders as a precursor to the natural hormone testosterone. This conversion requires naturally occurring enzymes in the body. Side effects are not uncommon, as prohormones can also convert further into DHT and estrogen. To deal with this, many supplements also have aromatase inhibitors and DHT blockers such as chrysin and 4-androstene-3,6,17-trione. To date most prohormone products have not been thoroughly studied, and the health effects of prolonged use are unknown. Although initially available over the counter, their purchase was made illegal without a prescription in the US in 2004, and they hold similar status in many other countries. They remain legal, however, in the United Kingdom and the wider European Union. Their use is prohibited by most sporting bodies.
Forbes, S. C., Sletten, N., Durrer, C., Myette-Côté, E , Candow, D., & Little, J. P. (2017, June). Creatine monohydrate supplementation does not augment fitness, performance, or body composition adaptations in response to four weeks of high-intensity interval training in young females. Human Kinetics Journals, 27(3), 285-292. Retrieved from
The creatine transporter is a sodium[139][140] and chloride[141][142] dependent membrane-associated transporter that belongs to the Na+/Cl-dependent family of neurotransmitter transporters.[143] In muscle cells and most other cell types,[131][141] 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.[144] A related gene encoding a creatine transporter variant has also been identified at 16p11.1 that is expressed exclusively in the testes.[145] These two transporters share 98% homology.[144][145]
Creatine is a hydrophilic polar molecule that consists of a negatively charged carboxyl group and a positively charged functional group [64]. The hydrophilic nature of creatine limits its bioavailability [65]. 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 [65]. Spillane et al [65] 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 [65] 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.