Microsoft word - creatin.doc

may contribute to enhanced freediving performance Creatine metabolism and mechanisms related to anaerobic performance
Creatine is one of the most common supplements amongst athletes today and several studies
have shown positive effects on anaerobic performance.
Adenosintriphosphate (ATP) is the molecule used as energy in the cells. During an
anaerobic activity, the muscles first use the available stores of ATP which are hydrolysed
during the process with the production of ADP, inorganic phosphate (Pi) and a hydrogen ion
(H+). The stores are limited and have to be regenerated. The molecule available for this
purpose is phosphocreatine (PCr), a high energy molecule which donates a phosphate group
to ADP and contributes to the regeneration of ATP Figure 1. The enzyme responsible for this
reaction is creatine kinase. This rapid utilization effectively buffers the momentary lag in
energy production from the glycolysis (1), which contributes to the major proportion of
energy during anaerobic activities. There are several mechanisms proposed for the induced
anaerobic capacity as a result of creatine supplementation. Apart from the obvious increased
capacity to regenerate ATP and stored energy in the muscle cell due to the increased levels of
PCr, it has been proposed that an increased rate in the resynthesis of PCr between the exercise
bouts is responsible to the increased capacity. Following high intensity exercise
approximately half of the pre-exercise muscle PCr content is restored within one minute of
recovery, but a complete restoration of the PCr pool takes up to 5-6 minutes (2). This
emphasizes the importance of rest between the apneas to allow restoration of PCr to take
A third mechanism suggested is that creatine supplementation contributes to a buffering
effect on muscle acidity. As mentioned previously, anaerobic activity contributes to the
formation of lactate which lowers the pH due to the dissociation of hydrogen ions (H+). The
increased acidity inhibits the enzyme phosphofructokinase which slows down the glycolysis
as a result. The low pH also has the ability to displace calcium from troponin, interfering with
muscle contraction and stimulate pain receptors. This has a negative effect on high intensity
exercise. The resynthesis of ATP by creatine kinase using PCr, consumes H+ which has a
buffering effect on the acidity and allow the muscle to accumulate more lactic acid before
reaching a fatigue inducing pH. Another positive effect observed during supplementation is an
increased muscle glycogen content (3).
Creatine is an osmotically active substance, meaning that a higher level of creatine in the
muscle cell leads to a higher amount of water entering the cell (4). Due to this, an increased
weight of 1-3 kg can be observed during supplementation of creatine.
Creatine is continually broken down and converted to its metabolic by-product creatinine,
this at an almost steady rate of ~2% of the total Creatine content per day (5). The creatinine
diffuses out of the muscle cells and is excreted by the kidneys into the urine.
Brain function
Creatine also plays a major role in the brain function. A study showed that in mice in which
both mitochondrial creatin kinase and brain-specific kinase were knocked out showed a
number of neurological impairments, including severely diminished spatial learning (6).
Vegetarians obtain very little dietary creatine and vegans virtually none. Essentially all of
their creatine has to be synthesised in the body. The endogenous synthesis seems to be
insufficient in these subjects since ingestion of vegetarian diets is associated with decreased
serum and muscle creatine levels (7;8). Interestingly, a study by Rae et al. performed at
vegans and vegetarians showed that creatine supplementation significantly improved their
performance on a number of cognitive tests (9).
Creatine also seems to have neuroprotective properties which may be of interest for the
freediver. In a recent study, mice were fed a diet supplemented with creatine for three weeks
and then underwent transient focal cerebral ischemia via occlusion of the cerebral middle
artery for 45 min. Dietary creatine supplementation reduced the infarct volume of these mice
by about 40% (10).
Creatine also exerts direct antioxidant effects, particularly towards superoxide and
peroxynitrite (11).
Creatine for freedivers?
For the freediver, supplementation with creatine may have positive effects on the performance
due to the slightly elevated stores of energy in the muscle cells before performing an apnea.
As mentioned above, supplementation may also have neuroprotective properties.
Optimal effect and muscle accumulation
The transport of creatine into the muscle cells is enhanced by insulin. Therefore, creatine
should be ingested together with some carbohydrates for optimal uptake (12).
Interestingly, exercise is a potent stimulus for creatine uptake by the skeletal muscle. This
was showed in a study where a single leg was exercised, resulting in appreciably more
creatine uptake than in the unexercised contralateral leg (13).
Caffeine seems to totally negate the ergogenic effects of creatine (14). Therefore athletes
who load creatine should refrain from caffeine containing products for several days before
Usually 20-25g/day of creatine monohydrate, divided into 4-5 doses, administered for 5-7
days are used during the loading phase, followed by maintenance doses of 2-5g per day.
Individuals with suspected renal malfunction should refrain from creatine supplementation
due to the potential for exacerbating the disorder (15). In healthy subjects, the renal function
seems to remain normal with cronic creatine use (16). Creatinine is commonly used as a
marker for the renal function where high levels in serum indicate an impaired function. One
method used in clinical laboratories to determine the creatinine levels is an enzymatic
conversion of creatinine to creatine of which the concentration is subsequently determined.
Because of the high serum concentration of creatine in subjects taking creatine supplement,
this method is not suitable since the levels appear higher than they actually are (17). This may
have contributed to the anecdotal renal dysfunction attributed to creatine supplementation.
Fig. 1. The regeneration of ATP by creatine kinase 1. Greenhaff PL. Creatine and its application as an ergogenic aid. Int.J.Sport Nutr. 2. Balsom PD, Soderlund K, Ekblom B. Creatine in humans with special reference to creatine supplementation. Sports Med. 1994;18:268-80. 3. van Loon LJ, Murphy R, Oosterlaar AM et al. Creatine supplementation increases glycogen storage but not GLUT-4 expression in human skeletal muscle. Clin.Sci.(Lond) 2004;106:99-106. 4. Wyss M, Kaddurah-Daouk R. Creatine and creatinine metabolism. Physiol Rev. 5. Wyss M, Kaddurah-Daouk R. Creatine and creatinine metabolism. Physiol Rev. 6. Streijger F, Oerlemans F, Ellenbroek BA, Jost CR, Wieringa B, Van der Zee CE. Structural and behavioural consequences of double deficiency for creatine kinases BCK and UbCKmit. Behav.Brain Res. 2005;157:219-34. 7. Lukaszuk JM, Robertson RJ, Arch JE et al. Effect of creatine supplementation and a lacto-ovo-vegetarian diet on muscle creatine concentration. Int.J.Sport Nutr.Exerc.Metab 2002;12:336-48. 8. Delanghe J, De Slypere JP, De Buyzere M, Robbrecht J, Wieme R, Vermeulen A. Normal reference values for creatine, creatinine, and carnitine are lower in vegetarians. Clin.Chem. 1989;35:1802-3. 9. Rae C, Digney AL, McEwan SR, Bates TC. Oral creatine monohydrate supplementation improves brain performance: a double-blind, placebo-controlled, cross-over trial. Proc.Biol.Sci. 2003;270:2147-50. 10. Prass K, Royl G, Lindauer U et al. Improved reperfusion and neuroprotection by creatine in a mouse model of stroke. J.Cereb.Blood Flow Metab 2007;27:452-9. 11. Lawler JM, Barnes WS, Wu G, Song W, Demaree S. Direct antioxidant properties of creatine. Biochem.Biophys.Res.Commun. 2002;290:47-52. 12. Green AL, Hultman E, Macdonald IA, Sewell DA, Greenhaff PL. Carbohydrate ingestion augments skeletal muscle creatine accumulation during creatine supplementation in humans. Am.J.Physiol 1996;271:E821-E826. 13. Harris RC, Soderlund K, Hultman E. Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation. Clin.Sci.(Lond) 1992;83:367-74. 14. Vandenberghe K, Gillis N, Van Leemputte M, Van Hecke P, Vanstapel F, Hespel P. Caffeine counteracts the ergogenic action of muscle creatine loading. J.Appl.Physiol 1996;80:452-7. 15. Pritchard NR, Kalra PA. Renal dysfunction accompanying oral creatine supplements. 16. Poortmans JR, Francaux M. Long-term oral creatine supplementation does not impair renal function in healthy athletes. Med.Sci.Sports Exerc. 1999;31:1108-10. 17. Groeneveld GJ, Beijer C, Veldink JH, Kalmijn S, Wokke JH, van den Berg LH. Few adverse effects of long-term creatine supplementation in a placebo-controlled trial. Int.J.Sports Med. 2005;26:307-13.



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