Macrophages are known to express creatine kinase[290] and take creatine up from a medium through a sodium dependent mechanism (likely the creatine transporter) in a saturable manner,[435] with a second component that requires there to be no concentration gradient to work against (likely passive diffusion) but this effect tends to only account for up to 10% of total uptake in the physiological range (20-60µM).[435] Supraphysiological range was not tested.

A study using creatine at 0.02% of a face cream (confounded with 8% glycerol and 0.4% Guarana) was able to exert a skin-tightening effect over 6 weeks, reducing wrinkles and jowl volume.[541] Combination therapy has also been used with creatine and folic acid (both in vitro[543] and in vivo), resulting in increased skin firmness and reduced coarse and fine wrinkles.[544]
The lower the rep range (and therefore the higher the intensity and the heavier the weight), the more rest there should be between sets. So most of the time, exercises being done in the 5-8 rep range need longer rest periods than exercises being done in the 8-10 rep range, which need longer rest periods than exercises being done in the 10-15 rep range.
Kidney damage (from anything) will cause high levels of creatinine in blood, and creatine can also increase blood creatinine levels in a manner that is not due to damaging the kidneys. This results in a false positive when trying to diagnose kidney damange when the subject also supplements creatine, and does not signify any actual damage to the kidneys.
When creatine is increased in the fetus (from maternal supplementation of 5% creatine), the fetus has a greater chance of survival and increased growth rates to a level not significantly different than vaginal birth.[531] Protection from hypoxia has also been noted in the offspring’s diaphragm (through preserved muscle fiber size),[533] kidneys,[534] and neural tissue (due to less oxidation in the brain and less cellular apoptosis).[535]
This cellular influx may also decrease protein oxidation rates, which leads to increases in nitrogen balance and indirectly increases muscle mass.[379] This lowering of protein oxidation is from signaling changes caused vicariously through cell swelling[380][381] and appears to upregulate 216 genes[378] in a range of 1.3 to 5-fold increases, with the largest increase seen in the protein involved in satellite cell recruitment, sphingosine kinase-1. Most importantly for muscle hypertrophy, the protein content of PKBa/Akt1, p38 MAPK, and ERK6 increased 2.8+/-1.2 fold.[378] Sixty-nine genes are also downregulated after creatine supplementation, to less notable degrees.
Some bodybuilders use drugs such as anabolic steroids and precursor substances such as prohormones to increase muscle hypertrophy. Anabolic steroids cause hypertrophy of both types (I and II) of muscle fibers, likely caused by an increased synthesis of muscle proteins. They also provoke undesired side effects including hepatotoxicity, gynecomastia, acne, the early onset of male pattern baldness and a decline in the body's own testosterone production, which can cause testicular atrophy.[42][43][44] Other performance-enhancing substances used by competitive bodybuilders include human growth hormone (HGH), which can cause acromegaly.
Recommended dose: The fastest way to increase muscle creatine stores is to follow the loading method of 20 grams per day for 5-7 days, followed by the standard maintenance dose of 5 grams per day. However, a lower dose of 5 grams for 28 days will also increase creatine stores without causing the 2-4 pound weight gain typically seen with a loading protocol.
A: First, you have to realize that when one is gaining weight it’s nearly impossible (steroid discussion aside) to gain solely muscle without the acquisition of some body fat as well. That being said though, you can improve thedistribution of lean body mass to fat mass by ensuring that your calorie consumption isn’t too aggressive (i.e. 1000+ over your BMR). Also, it should go without saying, but you need to be training hard while focusing on progressive overload to ensure that the calories you’re ingesting are actually going towards muscle growth. You shouldn’t be neglecting cardiovascular work either; both HIIT and LISS each play a role in enhancing mitochondrial density, balancing neurotransmitters, improving oxidative capacity, and influencing brain plasticity.
There is a great amount of research published on creatine supplementation; protocols of administration, forms of creatine, as well as potential side effects. Despite this, the mechanisms by which creatine acts in the human body to improve physical and cognitive performance are still not clear. The main objectives of this review are to analyze the more recent findings on the effects and mechanisms of creatine supplementation in sports and health. As a secondary purpose, we will analyze the most recommended protocols of ingestion and its potential side effects.
It was later noted that creatine was able to nonsignificantly augment various proinflammatory cytokines (CCL2, iNOS, ICAM-1, TGF-β, TIMP-1) and the presence of eosinophils in lung tissue, as well as to per se cause lung infiltration of these immune cells without requiring the presence of the allergen.[442] Neutrophils and macrophages were unaffected,[442] reflecting the past study of no influence on macrophages,[440] but the only instance where creatine appeared to either significantly add to ovalbumin or to per se induce statistically significant increases were in IL-5 secretion and goblet cell infiltration, although VCAM-1 expression was close. While creatine per se increased nF-κB activity, it suppressed the ovalbumin-induced increase.[442]
In well-trained endurance runners, creatine (with glycerol for hyperhydration) caused a relatively large increase in body weight gain (0.90+/-0.40kg) and water weight (0.71+/-0.42L) but failed to negatively influence performance over 30 minutes in the heat.[3] This failure to improve physical performance in the heat with creatine loading (despite water retention) has been noted elsewhere.[346]
When you’re planning your high-protein meals, 20 grams of protein is the optimal amount generally accepted for muscle growth. Research has found that the body doesn’t use much more than 20 grams for muscle-building at any one sitting. Around 80 grams of protein per day (or, four meals containing 20-grams of protein each) is about right for most people.
According to the two meta-analyses on the topic, creatine significantly increases power when supplemented in both sexes over a period of time up to 8 weeks, during which improvement over placebo is maintained, rather than being enhanced further. The rate at which power is derived from a resistance training regimen appears to be up to 78.5% greater with creatine relative to placebo, and in active trained men who are naive to creatine, this can be quantified at about 7kg for the bench press and 10kg for the squat over 8 weeks.
In the stomach, creatine can degrade by about 13% due to the digestive hormone pepsin, as assessed by simulated digestion.[127] Although creatinine is a known byproduct of creatine degradation, simulated gastric digestion did not increase creatinine levels, indicating that other breakdown products were formed. However, creatinine was noted to increase in the presence of pancreatin, a mixture of pancreatic enzymes.[127] 
This period also saw the rise of anabolic steroids in bodybuilding and many other sports. In bodybuilding lore, this is partly attributed to the rise of "mass monsters", beginning with Arnold Schwarzenegger, Sergio Oliva, and Lou Ferrigno in the late 1960s and early 1970s, and continuing through the 1980s with Lee Haney, the 1990s with Dorian Yates, Ronnie Coleman, and Markus Rühl, and up to the present day. Bodybuilders such as Greg Kovacs attained mass and size never seen previously but were not successful at the pro level. Others were renowned for their spectacular development of a particular body part, like Tom Platz or Paul Demayo for the leg muscles. At the time of shooting Pumping Iron, Schwarzenegger (while never admitting to steroid use until long after his retirement) said that "you have to do anything you can to get the advantage in competition".[citation needed] He would later say that he does not regret using anything.[8]

Cornelissen, V. A., Defoor, J. G., Stevens, A., Schepers, D., Hespel, P., Decramer, M., Mortelmans, L., Dobbels, F., Vanhaecke, J., Fagard, R. H., and Vanhees, L. Effect of creatine supplementation as a potential adjuvant therapy to exercise training in cardiac patients: a randomized controlled trial. Clin.Rehabil. 2010;24(11):988-999. View abstract.


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.
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