Elsewhere, it has been noted that in chronic progressive external ophthalmoplegia (CPEO, a progressive weakening of the muscles around the eye and a mitochondrial disorder), there was a failure of creatine supplementation to benefit symptoms when subjects were provided 20g daily for four weeks.[483] Creatine supplementation failed again at 150mg/kg for six weeks in people with either CPEO or another disorder associated with single gene deletions affecting the eyes (Kearns–Sayre syndrome, KSS) in improving muscular function.[484]
In a study on Alpha-Lipoic Acid, 1,000mg of ALA paired with 100g sucrose and 20g creatine monohydrate was more effective in increasing muscular creatine levels relative to creatine alone and creatine combined with sucrose.[600] This apparent augmentation of creatine uptake into muscle cells was used alongside a loading period. Another study investigating a nutrient mixture (150g glucose, 20g creatine, 2g/kg bodyweight glycerol) on heat tolerance in trained athletes found that replacing one third (50g) of the glucose with 1g ALA resulted in no significant differences between groups (in regard to heat tolerance and cardiovascular performance) despite the reduction of 50g carbohydrate.[601]
The last survivors of the pro-hormone supplements, which were removed from sale last January, estrogen-blocking supplements aren't pro-hormones but do inhibit the enzyme aromatase, which converts androgens into estrogens. In normal men that enzyme is ubiquitous, being present in such tissues as muscle, brain and skin. About 20 percent of the free testosterone circulating in the blood is converted into estrogen by way of aromatase.

Taking high doses of creatine might harm the kidneys. Some medications can also harm the kidneys. Taking creatine with medications that can harm the kidneys might increase the chance of kidney damage.

Some of these medications that can harm the kidneys include cyclosporine (Neoral, Sandimmune); aminoglycosides including amikacin (Amikin), gentamicin (Garamycin, Gentak, others), and tobramycin (Nebcin, others); nonsteroidal anti-inflammatory drugs (NSAIDs) including ibuprofen (Advil, Motrin, Nuprin, others), indomethacin (Indocin), naproxen (Aleve, Anaprox, Naprelan, Naprosyn), piroxicam (Feldene); and numerous others.

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]
Drink plenty of water throughout the day, especially in the hours leading up to your workout. This can help you feel full and reduce hunger pangs. During training, drink about 8 ounces every 15-20 minutes, more when it's hot and humid. The reason is simple: Your performance quickly begins to suffer when the body is dehydrated just 1%-–2%. And if you wait till you feel thirsty, you've waited too long. A flavorful, low-calorie sports drink is a great way to hydrate. Try drinking fluids stored at cooler temperatures; studies show that people consume more when the liquid is colder.
Previous investigations have shown that a single dose of CM (8 grams) increased the number of repetitions performed during an upper-body resistance training protocol and reduced soreness at 24 and 48 hours post-exercise (compared to a placebo).7 Recently, researchers from Mississippi State University found that a single dose of CM (8 grams) significantly increased the number of lower-body repetitions compared to a placebo group.[8]

Jager et al [60] observed 1.17 and 1.29 greater peak plasma creatine concentration 1 hour after ingesting creatine pyruvate compared to isomolar amount of CM and creatine citrate respectively. However time to peak concentration, and velocity constants of absorption and elimination, was the same for all three forms of creatine. Although not measured in this study it is questionable that these small differences in plasma creatine concentrations would have any effect on the increase of muscle creatine uptake. Jäger et al [61] investigated the effects of 28-days of creatine pyruvate and citrate supplementation on endurance capacity and power measured during an intermittent handgrip (15 s effort per 45s rest) exercise in healthy young athletes. The authors used a daily dose protocol with the intention to slowly saturate muscle creatine stores. Both forms of creatine showed slightly different effects on plasma creatine absorption and kinetics. The two creatine salts significantly increased mean power but only pyruvate forms showed significant effects for increasing force and attenuating fatigability during all intervals. These effects can be attributed to an enhanced contraction and relaxation velocity as well as a higher blood flow and muscle oxygen uptake. On the other hand, the power performance measured with the citrate forms decreases with time and improvements were not significant during the later intervals. In spite of these positive trends further research is required about the effects of these forms of creatine as there is little or no evidence for their safety and efficacy. Furthermore the regularity status of the novel forms of creatine vary from country to country and are often found to be unclear when compared to that of CM [62].


It is known that intracellular energy depletion (assessed by a depletion of ATP) stimulates AMPK activity in order to normalize the AMP:ATP ratio,[333][334] and when activated AMPK (active in states of low cellular energy[335] and colocalizes with creatine kinase in muscle tissue[336]) 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.[334] 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.[334][336][337]
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