Creatine side effects: Supplementation with creatine is safe - but it works best for

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works best for men
Despite the extensive use of creatine monohydrate for performance enhancement, few studies have examined the potential side effects of supplementation and none has directly compared the response to supplementation in men and women. This gap in knowledge has now been filled by a Canadian study of young, healthy, physically active men and women, which showed no adverse effects of short-term treatment but greater body-building benefits for men than for women.
Fifteen men and 15 women were randomly assigned to five days' supplementation with 20g per day of either creatine monohydrate (CrM) or a similar-looking inactive substance (placebo) after extensive pre-trial checks, including measurement of body composition, blood pressure and maximal strength. On day six they returned to the lab for retesting. Blood pressure was unaffected by supplementation, and blood tests suggested there were no effects on kidney function. Plasma levels of the muscle enzyme creatine kinase, which is thought to have potentially damaging effects at increased levels, was unaffected by treatment.

As far as body composition was concerned, there was no effect of treatment on percentage body fat but clear increases in both total body mass (TBM) and fat-free mass (FFM). However, these changes were much smaller for women than for men: men increased both TBM and FFM by 2%, while for women the respective increases were only 0.8 and 1.0%. CrM treatment had no effect on grip strength during forearm tests and no significant effect on resting and post-exercise blood lactate levels. The implication of these findings is that creatine monohydrate may be less useful as a performance-enhancing aid for women than for men. 'It was not anticipated a priori that such large sex differences would exist in response to CrM loading, given that the subjects were matched for age and training status,' explain the researchers. They point out that it is possible the women had higher muscle concentrations of total creatine before supplementation, which might have reduced its effectiveness.

In terms of safety CrM gets the thumbs-up, although the potential side effects of long-term supplementation have yet to be examined. In addition to its benefits for athletes, CrM could also be used to treat people with muscle atrophy and other wasting conditions.

Med Sci Sports Exerc 2000 Feb 32 (2) 291-6

Isabel Walker

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The role of creatine in preventing muscular fatigue and boosting performance has preoccupied scientists for some time. But now it seems they are turning their attention to its potential for alleviating mental (or central) fatigue – an equally beneficial effect.

A team of Japanese researchers randomly assigned 24 young healthy volunteers (19 men and five women) to five days’ supplementation with 8g of either creatine monohydrate or placebo tablets per day. Before and after supplementation they completed a serial calculation task designed to reflect mental fatigue. At the same time oxygenation changes within the brain that are associated with mental fatigue were measured by a unique non-invasive technique known as near infrared spectroscopy (NIRS). Analysis of the results showed that after supplementation the creatine group experienced less mental fatigue when repeatedly performing the simple mathematical calculations than the placebo group. Study of the NIRS data showed that task-evoked increase of cerebral oxygenated haemoglobin in the brains of creatine-supplemented subjects was significantly reduced – a finding which is compatible with increased oxygen utilisation in the brain. ‘Because oral ingestion of creatine [has been] reported to increase creatine content in the brain… the effect of creatine on mental fatigue may be mediated by its effect on energy metabolism in the brain,’ report the researchers. ‘Although it cannot be totally ruled out that reduced muscle fatigue, rather than mental fatigue, contributed to the observed change in the performance of serial calculation task, haemoglobin oxygenation changes associated with creatine supplement suggested that this was mediated by its effect on the brain. ‘Although the interpretations are speculative and the data are not conclusive, our experiment may suggest a new line of approach to reduction of mental fatigue involving creatine.’

Neurosci Res 2002 Apr(4), pp 279-85

Isabel Walker

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Factors modifying creatine accumulation in human skeletal muscle:........................................... .................................................. .........

by Paul Greenhaff, School of Biomedical Sciences, University Medical School, Nottingham

The ingestion of 5g of creatine (Cr) in solution will raise the plasma Cr concentration from ~40 umol/l to 600 – 800 umol/l within 1 hr and plasma levels then decrease to close to basal over the subsequent 5 hrs (Harris et al. 1992, Green et al. 1996a). Repeating this procedure on four evenly spaced occasions each day for five days can increase the muscle total Cr (TCr) store by up to 40%. This increase is comprised of changes in both free Cr and phosphocreatine (PCr), with the magnitude of increase in the former being the largest (Harris et al. 1992, Greenhaff et al. 1994). The variation between individuals in the magnitude of muscle TCr increase is marked, with the extent of uptake being inversely related to the initial muscle TCr content (Harris et al. 1992, Greenhaff et al. 1994). The reasons for the large variation between subjects in the magnitude of Cr accumulation during supplementation are unknown and require further investigation.
The majority of muscle Cr accumulation occurs within the initial two days of loading and muscle Cr accumulation is saturated following five days of supplementation with 4 x 5g doses (Harris et al. 1992, Hultman et al. 1996). If Cr ingestion is stopped following loading, muscle Cr stores decline gradually and basal levels are reached after about four weeks (Febbraio et al. 1995, Hultman et al. 1996). Ingesting Cr at a rate of 3g per day will increase muscle Cr content but the time-course of change is slower, i.e. it takes 30 days to reach muscle TCr values similar to those observed after five days of 20g/day Cr ingestion (Hultman et al. 1996). Following loading, elevated muscle Cr stores can be maintained for at least one month by ingesting 2g of Cr per day in a single dose (Hultman et al. 1996). This maintains muscle Cr delivery at slightly above the rate of muscle Cr degradation to creatinine. Urinary creatinine output increases by about 20% which parallels the increase in muscle Cr content (Hultman et al. 1996).

Sub-maximal exercise performed prior to Cr ingestion can augment muscle Cr accumulation by about 10%, but again the variation in response is marked when comparing individuals (Harris et al. 1992).

Creatine plus carbohydrates
Muscle Cr accumulation can be substantially augmented by ingesting Cr in combination with large quantities of simple carbohydrates (Green et al. 1996b). This reduces the variation in responses between individuals and also outweighs any stimulatory effect exercise has on muscle Cr accumulation (Green et al. 1996a, 1996b). Muscle Cr accumulation is thought to be augmented as a result of insulin stimulating muscle sodium pump activity, and thereby sodium-dependent Cr transport. Recent evidence has demonstrated that it will require in the region of 100g of simple carbohydrates to be ingested to achieve an insulin-mediated stimulation of muscle Cr transport (Steenge et al. 1998). In practical terms, this will be difficult for individuals to achieve as the ingestion of such a large quantity of carbohydrate is at the limit of palatability. There are no data currently available to demonstrate the time-course of muscle Cr accumulation when Cr is ingested in the presence of large quantities of carbohydrate, i.e. how quickly is muscle Cr uptake saturated? This may be of significant practical importance.

A muscle Cr transport protein has recently been identified and it has been shown that its expression is down-regulated in rat skeletal muscle following six months of supra-physiological amounts of Cr supplementation (Guerrero-Ontiveros and Wallimann, 1998). Whether a similar response occurs in humans is unknown, as is the consequences of chronic Cr ingestion on the muscle Cr transport mechanism, i.e., why does the muscle become desensitised to Cr as a result of chronic ingestion? (For more on creatine and other ergogenics, see the middle pages of this issue)

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AND YET, ANOTHER CREATINE ARTICLE


While there's little doubt that creatine supplements can aid short-duration, high-intensity exertions, there's been considerable debate about whether extra intakes of the amino acid might help endurance athletes during efforts which last for more than a few minutes.

Muscle cells use creatine primarily to form creatine phosphate, a high-octane chemical which provides the energy needed for short, fast efforts, but those who are sceptical about creatine's ability to enhance endurance performance point out that the supply of creatine inside muscles is fairly limited. In fact, an exertion as brief as a 400-metre run can drastically deplete leg muscles of their creatine phosphate. Since most of a muscle cell's creatine phosphate can be wiped out after just 60 seconds of exercise, how could creatine aid performance in longer efforts like a 5K race or a 20-minute cycle competition?
The pro-creatine people counter that creatine phosphate is not depleted as rapidly during less intense exertions and that extra creatine phosphate might be helpful for fast starts during medium-distance races, for 'kicks' at the ends of races, and for uphill surges during exercise on hilly terrain. They also note that since creatine phosphate 'carries' energy to locations inside muscle cells where it is critically needed to sustain muscle contractions, surplus creatine might lead to improved fatigue resistance during endurance exercise.

However, these contentions have been pretty much theoretical until now. Brand-new research with creatine supplements and endurance runners has been carried out, and the news is not good for creatine advocates. In the current investigation, which was completed at the famed Karolinska Institute in Stockholm, Sweden, nine well-trained runners ingested five grams of creatine monohydrate four times per day (20 grams per day) for six days, while nine other experienced runners consumed a glucose placebo. After the six-day period, the runners completed a six-kilometre race over undulating terrain and (on a second day) a high-speed treadmill run to exhaustion at a velocity slightly faster than their best one-mile race speed.

Strangely enough, although neither creatine- nor placebo-group members were able to improve their performances during the treadmill efforts, runners actually fared slightly worse during the 6K forest trial after creatine supplementation (they required about 25 more seconds to complete the course). Following creatine ingestion, they also produced considerably more blood lactate during the sizzling treadmill effort.

Why did creatine ingestion lead to slightly inferior 6K performances - and higher blood-lactate levels at one-mile race pace? Previous research has indicated that creatine supplementation may produce a slight muscle-building effect, or - more specifically - an expansion in the size of type 11 ('fast twitch') muscle fibres. Although the Karolinska researchers didn't measure muscle-cell diameters, they did find that the creatine supplementers boosted body weight by about 1 per cent, while the placebo-takers maintained a constant weight. It's possible that this increased weight could have been due to greater muscle bulk and could have led to slower performances during the 6K. (Especially intriguing is the fact that average 6K time and body weight each expanded by about 1 per cent.) The higher lactate during treadmill running could have been due to the increased girth of the lactate-producing type 11 fibres - or to the need to do more anaerobic work to push the runners' heavier bodies through the rugged test.




Regardless of what actually happened to the creatine consumers, the results weren't encouraging for creatine supporters. The Swedish scientists involved in the study concluded that the performance-enhancing effects of creatine supplementation are probably restricted to short duration, high-intensity exercise. 'Creatine Supplementation Per Se Does Not Enhance Endurance Exercise Performance, Acta Physiologica Scandinavica, vol. 149, pp. 521-523, 1993.

Vitamin E supplements linked with lower risk of heart disease in men and women
Can the intake of increased amounts of vitamin E lower your risk of coronary artery disease - the number-one health problem in both Great Britain and the United States? Some scientists have thought so, since vitamin E blocks a chemical reaction which might shove increased amounts of low-density lipoprotein (LDL) into the walls of your heart's arteries. LDL can block the free flow of oxygenated blood to your hard-working heart muscle and may have a number of damaging effects on artery walls.

Now, there's evidence that vitamin E supplements can indeed lower the chances of cardiovascular problems. In a unique study carried out by researchers at Harvard University, 39,910 health professionals (dentists, veterinarians, pharmacists, optometrists, podiatrists, and osteopathic doctors) aged 40 to 75 were studied between 1986 and 1990. At the beginning of the study, the men were free of heart disease, high blood-cholesterol levels, and diabetes. Detailed questionnaires revealed the nutrient compositions of their diets.

During the four-year follow-up, 667 men (almost 2 per cent) developed coronary artery problems, but the disease was most common among men who did not take vitamin E supplements. For example, individuals who supplemented their normal diets with at least 100 IU of vitamin E per day had about a 37-per cent lower risk of developing heart disease, compared to men who took no supplements.

Some scientists have suggested that vitamin C and carotene (a yellowish-orange compound in fruits and vegetables which your body readily converts to vitamin A) might also lower cardiovascular risk, but a high intake of vitamin C had no protective effect whatsoever in the Harvard study. High carotene consumption didn't help individuals who had never smoked, but taking in more than about 14,000 IU per day lowered the risk of heart problems by 70 per cent among current smokers, and the risk reduction was about 40 per cent for former smokers.

Although the Harvard study doesn't prove that there's a cause-and-effect relationship between higher vitamin E intake and a reduced risk of heart maladies, the link between E and better heart health is intriguing, especially since a second study carried out by Harvard researchers detected lower rates of coronary disease among women who were taking vitamin E supplements. In this second research project, 87,245 female nurses aged 34 to 59 were studied between 1980 and 1988. The women were initially free of both heart disease and cancer.

During the eight-year research period, 552 women (less than 1 per cent) developed heart disease, but again the cardiac difficulties took place at a much higher rate in women who didn't supplement with E. Women who ingested at least 200 IU of vitamin E per day for at least two years enjoyed a 40-per cent lower risk of heart disease, compared to non-supplementers. This was about the same benefit attained by the E-taking men. The bottom line is that taking in 200-400 IU of supplemental vitamin E per day appears to present few health hazards and may keep blood flowing freely through your coronary arteries. 'Vitamin E Consumption and the Risk of Coronary
Heart Disease in Men,' The New England Journal of Medicine, vol. 328, pp. 1450-1456, 1993 and
'Vitamin E Consumption and the Risk of Coronary Disease in Women,' The New England Journal of Medicine, vol. 328, pp. 1444-1449, 1993