Creatine pyruvate (also known as creatine 2-oxopropanoate) in an isomolar dose relative to creatine monohydrate has been shown to produce higher plasma levels of creatine (peak and AUC) with no discernible differences in absorption or excretion values.[83] The same study noted increased performance from creatine pyruvate at low (4.4g creatine equivalence) doses relative to citrate and monohydrate, possibly due to the pyruvate group.

Creatine supplementation has been noted to improve general wellbeing and health status (assessed by St George’s Respiratory questionnaire[582]) of people with COPD over two weeks loading (17.1g daily with carbohydrates) and ten weeks of 5.7g maintenance.[579] The studies that failed to find improvements with creatine supplementation on muscular performance also failed to find improvements in this rating scale, relative to placebo.[580][581]


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[233]) while possibly increasing dopaminergic activity (conversely seen to benefit activity in the heat[234]).[155]
In nonelite swimmers conducting an intermittent sprint protocol (Six 50m sprints every two minutes), supplementation of a creatine loading period was able to reduce the decrement in speed during the third sprint (2% decrement rather than a 5% decrement) but not the sixth sprint. There were no changes in plasma lactate or other biomarkers of fatigue.[396] When examining a single 50m sprint in amateur swimmers, a creatine loading period is able to reduce the time to complete the sprint by 4.6%, while it had no benefit for the 100m sprint.[397] When the loading phase was followed by three weeks maintenance in youth, there was no apparent benefit to sprint performance (50m sprint with five minutes rest followed by a 100m freestyle) despite benefits to a swim bench test (30s sprints with a five minute break in between).[398]
It has been argued that purposely overtraining for a brief period can be beneficial. One article published by Muscle & Fitness magazine stated that you can "Overtrain for Big Gains". It suggested that if one is planning a restful holiday and does not wish to inhibit their bodybuilding lifestyle too much, they should overtrain before taking the holiday, so the body can recuperate and grow during the prolonged rest period. Overtraining can be used advantageously, as when a bodybuilder is purposely overtrained for a brief period of time to super compensate during a regeneration phase. These are known as "shock micro-cycles" and were a key training technique used by Soviet athletes.[53]
Branched-chain amino acids (leucine, isoleucine, valine) play important roles in muscle building. Some researchers have found that following exercise, the branched-chain amino acids, especially leucine, increase the rate of protein synthesis and decrease the rate of protein catabolism (Blomstrand, 2006). The billion dollar supplement industry has been quick to respond; leucine supplements are widely available in health food stores, with a cost upwards of $50 per container. However, because the research findings are inconsistent and little is known about the safety of these products, the American Dietetic Association (soon to be renamed the Academy of Nutrition and Dietetics) advises against individual amino acid supplementation and protein supplementation overall (Rodriquez, 2009). It may be that food sources of these proteins and amino acids provide the same effect for a small fraction of the cost.

Creatine kinase is expressed in eyes. The eyes can take creatine up from the blood via two different transporters, the classic SCL6A8 (creatine transporter) and MCT12. It seems that expression of the receptors and accumulation of creatine occur in a relatively higher level in photoreceptors, which perceive color. Similarly to many other tissues, they appear to protect the cells during periods of low oxygen availability.


In the United States, the manufacturers of dietary supplements do not need to provide the Food and Drug Administration with evidence of product safety prior to marketing.[8] As a result, the incidence of products adulterated with illegal ingredients has continued to rise.[8] In 2013, one-third of the supplements tested were adulterated with unlisted steroids.[9] More recently, the prevalence of designer steroids with unknown safety and pharmacological effects has increased.[10][11]
Minor liver lesions (grade I, no grade II or III, pathology not indicative of toxicity) have been studied in SOD1 G93A transgenic mice (a research model for amyotrophic lateral sclerosis or ALS, but used in this study to assess a state of chronic pro-oxidative stress) for 159 days with 2% of feed intake and in CD-1 rats (seen as normal) over 56 days with 0.025-0.5mg/kg in CD-1 mice, although in Sprague-Dawley rats (normal controls) there were no significant differences noted even after 2% of feed intake for 365 days.[503] These observations appear to be due to the strain of the rodents used,[504][503] and human studies on amyotrophic lateral sclerosis (ALS; what the SOD1 G93A transgenic mice are thought to represent) lasting from nine to sixteen months with subjects supplementing with up to 10g of creatine daily have failed to find any abnormalities in serum biomarkers of liver or kidney health.[505][506][507]

Carbohydrates play an important role for bodybuilders. They give the body energy to deal with the rigors of training and recovery. Carbohydrates also promote secretion of insulin, a hormone enabling cells to get the glucose they need. Insulin also carries amino acids into cells and promotes protein synthesis.[26] Insulin has steroid-like effects in terms of muscle gains.[27] It is impossible to promote protein synthesis without the existence of insulin, which means that without ingesting carbohydrates or protein—which also induces the release of insulin—it is impossible to add muscle mass.[28] Bodybuilders seek out low-glycemic polysaccharides and other slowly digesting carbohydrates, which release energy in a more stable fashion than high-glycemic sugars and starches. This is important as high-glycemic carbohydrates cause a sharp insulin response, which places the body in a state where it is likely to store additional food energy as fat. However, bodybuilders frequently do ingest some quickly digesting sugars (often in form of pure dextrose or maltodextrin) just before, during, and/or just after a workout. This may help to replenish glycogen stored within the muscle, and to stimulate muscle protein synthesis.[29]
Synthesis primarily takes place in the kidney and liver, with creatine then being transported to the muscles via the blood. The majority of the human body's total creatine and phosphocreatine stores is located in skeletal muscle, while the remainder is distributed in the blood, brain, and other tissues.[17][18][20] Typically, creatine is produced endogenously at an estimated rate of about 8.3 mmol or 1 gram per day in young adults.[16][17] Creatine is also obtained through the diet at a rate of about 1 gram per day from an omnivorous diet.[17][18] Some small studies suggest that total muscle creatine is significantly lower in vegetarians than non-vegetarians, as expected since foods of animal origin are the primary source of creatine. However, subjects happened to show the same levels after using supplements.[21]
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