Creatine as a therapeutic supplement

• DEFINITION: Natural substance of the human body used as a supplement to treat specific health conditions.
• PRINCIPAL PROPOSED USE: Sports performance enhancement
• OTHER PROPOSED USES: Amyotrophic lateral sclerosis, cancer treatment support, chronic obstructive pulmonary disease, congestive heart failure, dermatomyositis, disuse atrophy following injury, mental function (following sleep deprivation), high triglycerides, Huntington’s disease, improved ratio of body fat to muscle, McArdle disease, mitochondrial illnesses, muscular dystrophy, myotonic dystrophy, Parkinson’s, polymyositis, schizophrenia, weight loss

Overview

Creatine is a naturally occurring substance that plays an important role in the production of energy in the body. The body converts it to phosphocreatine, a form of stored energy used by muscles.

Although the evidence for creatine is not definitive, it has the most evidence behind it among all the sports supplements. Numerous small double-blind studies suggest that it can increase athletic performance in sports that involve intense but short bursts of activity. The theory behind its use is that supplemental creatine can build up a reserve of phosphocreatine in the muscles to help them perform on demand. Supplemental creatine may also help the body make new phosphocreatine faster when it has been used up by intense activity.

Requirements and Sources

Although some creatine exists in the daily diet, it is not an essential nutrient because the human body can make it from the amino acids L-arginine, glycine, and L-methionine. Provided enough animal protein (the principal source of these amino acids) is consumed, the body will make all the creatine needed for good health.

Meat (including chicken and fish) is the most important dietary source of creatine and its amino acid building blocks. For this reason, vegetarian athletes may potentially benefit most from creatine supplementation.

Therapeutic Dosages

For bodybuilding and exercise enhancement, a typical dosage schedule starts with a loading dose of around 15 to 30 g daily (divided into 2 or 3 separate doses) for three to four days, followed by 2 to 5 g daily. Some authorities recommend skipping the loading dose. (By comparison, humans typically get only about 1 g of creatine in their daily diet.)

Creatine’s ability to enter muscle cells can be increased by combining it with glucose, fructose, or other simple carbohydrates; in addition, prior use of creatine might enhance the sports benefits of carbohydrate-loading. Caffeine may block the effects of creatine.

Therapeutic Uses

Creatine is one of the best-selling and best-documented supplements for enhancing athletic performance, but the scientific evidence that it works is far from complete. The best evidence points to potential benefits in forms of exercise that require repeated short-term bursts of high-intensity exercise; this has been seen more in artificial laboratory studies, though, than in studies involving athletes during normal sports performance. It might also be helpful for resistance exercise (weight training), although not all studies have found benefit.

Creatine has also been proposed as an aid to promote weight loss and to reduce the proportion of fat to muscle in the body, but there is little evidence that it is effective for this purpose. Preliminary evidence suggests that creatine supplements may be able to reduce levels of triglycerides in the blood. (Triglycerides are fats related to cholesterol that also increase the risk of heart disease when elevated in the body.) Creatine supplements might also help counter the loss of muscle strength that occurs when a limb is immobilized, such as following injury or surgery; however, not all results have been positive.

Studies, including small double-blind trials, inconsistently suggest that creatine might be helpful for reducing fatigue and increasing strength in various illnesses where muscle weakness occurs, including chronic obstructive pulmonary disease (COPD), congestive heart failure, dermatomyositis, Huntington’s disease, McArdle disease, mitochondrial illnesses, muscular dystrophy, and myotonic dystrophy.

One study claimed to find evidence that creatine supplements can reduce levels of blood sugar. However, because dextrose (a form of sugar) was used as the placebo in this trial, the results were somewhat questionable.

Evidence from animal and open human trials suggested that creatine improved strength and slowed the progression of amyotrophic lateral sclerosis (ALS), and for this reason, many people with ALS tried it. However, these hopes were dashed in 2003 when the results of a ten-month double-blind, placebo-controlled trial of 175 people with ALS were announced. Use of creatine at a dose of 10 grams (g) daily failed to provide any benefit in terms of symptoms or disease progression. Negative results were also seen in subsequent, slightly smaller studies. Creatine also does not appear to strengthen muscles in people with wrist weakness due to nerve injury.

Long-term use of corticosteroid drugs can slow a child’s growth. One animal study suggests that use of supplemental creatine may help prevent this side effect. Creatine has also shown some promise for improving mental function, particularly after sleep deprivation. However, in one small study, it showed no similar benefit in young adult subjects who were not sleep-deprived.

One study failed to find creatine helpful for maintaining muscle mass during treatment for colon cancer. Another study found little to no benefits in Parkinson’s disease, and another failed to find any benefit in schizophrenia.

According to MedlinePlus in 2024, the Natural Medicines Comprehensive Database reported that there was scientific evidence that taking creatine by mouth was possibly effective for improving athletic performance, disorders of creatine metabolism or transport, muscle strength, and age-related muscle loss (sarcopenia). The database also reported that orally administered creatine was possibly ineffective for amyotrophic lateral sclerosis (ALS), Huntington disease, and low bone mass (osteopenia).

Scientific Evidence

Exercise performance. Several small double-blind studies suggest that creatine can improve performance in exercises that involve repeated short bursts of high-intensity activity. For example, a double-blind study investigated creatine and swimming performance in eighteen men and fourteen women. Men taking the supplement had significant increases in speed when doing six bouts of 50-meter swims starting at three-minute intervals, compared with men taking a placebo. However, their speed did not improve when swimming ten sets of 25-yard lengths started at one-minute intervals. It may be that the shorter rest time between laps was not enough for the swimmers’ bodies to resynthesize phosphocreatine.

None of the women enrolled in the study showed any improvement with the creatine supplement. The authors of this study noted that women normally have more creatine in their muscle tissue than men do, so perhaps creatine supplementation (at least at this level) is not of benefit to women, as it appears to be for men. Further research is needed to fully understand this gender difference in response to creatine.

In another double-blind study, sixteen physical education students exercised ten times for six seconds on a stationary cycle, alternating with a thirty-second rest period. The results showed that individuals who took 20 g of creatine for six days were better able to maintain cycle speed. Similar results were seen in many other studies of repeated high-intensity exercise, although benefits are generally minimal in studies involving athletes engaged in normal sports rather than contrived laboratory tests. Isometric exercise capacity (pushing against a fixed resistance) also may improve with creatine, according to some studies.

In addition, two double-blind, placebo-controlled studies, each lasting twenty-eight days, provide some evidence that creatine and creatine plus beta hydroxymethyl butyrate (HMB) can increase lean muscle and bone mass. The first study enrolled fifty-two college football players during off-season training, and the other followed forty athletes engaged in weight training.

However, studies of endurance or non-repeated exercise have not shown benefits. Therefore, creatine probably will not help those running marathons or single sprints.

High triglycerides. A fifty-six-day double-blind, placebo-controlled study of thirty-four men and women found that creatine supplementation can reduce levels of triglycerides in the blood by about 25 percent. Effects on other blood lipids such as total cholesterol were insignificant.

Congestive heart failure. Easy fatigability is one unpleasant symptom of congestive heart failure. Creatine supplementation has been tried as a treatment for this symptom, with some positive results. A double-blind study examined seventeen men with congestive heart failure who were given 20 g of creatine daily for ten days. Exercise capacity and muscle strength increased in the creatine-treated group. Similarly, muscle endurance improved in a double-blind, placebo-controlled crossover study of twenty men with chronic heart failure. Treatment with 20 g of creatine for five days increased the amount of exercise they could complete before they reached exhaustion. These results were promising, but further study was needed.

Safety Issues

Creatine appears to be relatively safe. No significant side effects have been found with the regimen of several days of a high dosage followed by six weeks of a lower dosage. A study of one hundred football players found no adverse consequences during ten months to five years of creatine supplementation. However, medical professionals recommend that teens refrain from regularly using the supplement because studies had not determined the potential effect of creatine supplementation on development and it had often been observationally found that young adults do not follow dosage guidance as well. Contrary to early reports, creatine does not appear to adversely affect the body’s ability to exercise under hot conditions and might even be beneficial. The International Society of Sports Nutrition in the 2020s found no scientific evidence that using creatine causes any harmful effects on healthy individuals.

Dividing the dose may help avoid gastrointestinal side effects (diarrhea, stomach upset, and belching). In one study of fifty-nine male soccer players, administering two separate 5 g doses was associated with less diarrhea than a single 10 g dose.

However, there are some potential concerns with creatine. Because it is metabolized by the kidneys, fears have been expressed that creatine supplements could cause kidney injury, and there are two worrisome case reports. However, evidence suggests that creatine is safe for people whose kidneys are healthy to begin with and who do not take excessive doses. Furthermore, a one-year double-blind study of 175 people with amyotrophic lateral sclerosis found that use of 10 g of creatine daily did not adversely affect kidney function. Nonetheless, prudence suggests that individuals with kidney disease, especially those on dialysis, or people with conditions that could increase the risk of developing kidney disease should avoid creatine supplements.

Another concern is that creatine is metabolized in the body to the toxic substance formaldehyde. However, it is not clear whether the amount of formaldehyde produced in this way will cause any harm. A small number of deaths have been reported in individuals taking creatine, but other causes were most likely responsible.

It has also been suggested that use of oral creatine would increase urine levels of the carcinogen N-nitrososarcosine, but this does not seem to be the case. A few reports suggest that creatine could, at times, cause heart arrhythmias. As with all supplements taken in very high doses, it is important to purchase a high-quality form of creatine because contaminants present even in very low concentrations could conceivably build up and cause problems.

According to MedlinePlus in 2024, creatine may worsen mania in people with a bipolar disorder. The online resource also noted that taking creatine with caffeine may worsen symptoms of Parkinson disease, and that there was insufficient information regarding whether pregnant or breastfeeding people could safely use creatine.

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