Sports health screening: can creatine create a problem?

SPB explains how creatine works in the body and how supplementation could affect the validity of routine blood testing

Since first coming to light in the 1992 Barcelona Olympic Games, creatine has become one of the most popular sports supplements out there because - unlike many other so-called performance supplements – it actually does what it says on the tin! Found as a naturally occurring molecule found in ‘muscle foods’ such as meat and fish, creatine is also synthesised in the body from the amino acids arginine, glycine and methionine. The typical adult body contains around 120-140 grams of creatine, most of which is stored in the muscle tissue. Each day, around 2 grams of creatine is lost from the body (via the urine), which needs to be replenished either from biosynthesis or from the diet.

How does creatine work?

During very intense exercise, for example when sprinting, muscular ATP (the energy source that drives muscular contraction) is broken down much more rapidly than it can be regenerated via the aerobic system. However, muscles store a compound called creatine phosphate, which acts as a reservoir of high-energy phosphate. When ATP runs low, this creatine phosphate donates its high-energy phosphate to help regenerate ATP very rapidly, therefore prolonging the time to exhaustion.

Taking supplemental creatine has been shown to boost the regeneration of muscle ATP, helping to sustain high-energy bursts for longer and recover more rapidly between bursts⁽¹⁾. This in turn translates into better performance during intense exercise, and because it enables greater training intensities, also helps to produce a greater training response; eg increased muscle growth after resistance training. Studies show that creatine supplementation increases lean body mass as well as strength, power, and efficacy when engaging in short-duration, high-intensity exercise⁽²⁾.

An additional ergogenic effect of creatine supplementation is increased body/muscle mass. A meta-analysis showed that approximately 64% of studies measuring body mass and/or body composition noted a statistically significant increase in lean body mass due to creatine supplementation, even when subjects were not engaged in high-intensity training⁽³⁾. However, taking creatine in conjunction with a resistance training program yields significantly greater increases in body mass⁽⁴⁾.

Raising creatine levels in the body

Since creatine is well supplied in meat and fish, an athlete could in theory eat a large quantity (several kilos) of animal protein everyday in order to boost body creatine stores. However, this would of course be expensive, impractical and overload the body with protein and calories! Therefore, supplementing with pure creatine is a much better option. But how should this best be done?

The recommendations regarding dosing of creatine are very varied. An analysis of creatine doses garnered from published literature revealed that a wide range of intakes and supplementation protocols all produced favorable outcomes when engaging in resistance training for increasing lean muscle mass⁽⁵⁾. A 2013 review study recommended that a dose of 0.03 grams per kg of creatine per day (around 2.5 grams per day for an 80kg athlete) worked well as an ongoing maintenance dose when taken over an extended period from 4-6 weeks⁽⁶⁾. However, studies have reported on creatine usage for up to ten weeks⁽⁷⁾. To further complicate matters, many commercially available creatine supplements that recommend once-daily dosing appear intentionally vague regarding recommended frequency or duration of dosing. What we can say however is that athletes who do take creatine as a supplement will be ingesting and storing much higher levels in the body than athletes who do not, even if the diet is rich in meat/fish.

Creatine safety

In skeletal muscle, both creatine and phosphocreatine are gradually degraded to creatinine, which is exported to the blood and excreted in the urine⁽⁸⁾. Healthy kidneys therefore filter out this creatinine, which would otherwise increase in the blood. Because of the role of the kidneys in filtering out excess creatinine from the bloodstream, some researchers have expressed concern that taking creatine as a supplement over extended time periods could put the kidneys under stress, especially when creatine intakes are high. This concern seems reasonable; after all, it is prudent to be cautious when ingesting any dietary supplement or medication.

However, survey data indicates that creatine supplementation usage ranges between 8-74% in athletes and other exercising individuals⁽⁹⁾. Even using the low estimate of 8% of exercising individuals using creatine supplements, this indicates tens of millions of exposures across several decades. If the link between creatine supplementation and kidney health was valid, there would be an expected increase in kidney damage/renal dysfunction in low risk (ie young, physically fit, healthy) individuals since 1992, when creatine use first became popular. But after nearly 30 years of post-marketing surveillance, millions of exposures, and multiple clinical trials, no such evidence exists⁽¹⁰⁾. In summary, experimental and controlled research indicates that creatine supplementation, when ingested at recommended dosages, does not result in kidney damage and/or renal dysfunction in healthy individuals.

Creatine and blood testing

The evidence is clear; taken at the recommended dosages by fit, healthy individuals, creatine is safe and effective. However, it turns out that regular creatine users may find that routine blood test results could be affected by creatine use. This is something that the author can attest to from his recent personal experience!

A few weeks ago, I underwent routine blood testing as part of an overall health check-up. It was pleasing to find that all the tests were passed with flying colors – except one, which was the kidney function test. Kidney function is tested by measuring blood creatinine levels. Creatinine is considered a reliable marker of kidney function; it is continually produced in the body via the natural breakdown of protein and creatine (see figure 1), and therefore needs to be continually removed from the bloodstream by the kidneys to avoid excess levels, which could be toxic. In those with compromised kidney function, reduced creatinine clearance (ie higher levels in the bloodstream) is often a useful indicator.

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Fig 1: Creatine, phosphocreatine and creatinine

Creatine ingested in food/supplements and synthesized in the body can be converted to phosphocreatine, which muscles can use as a short-term high-energy fuel. However, both creatine and phosphocreatine are subject to continuous breakdown into creatinine, which needs to be cleared from the bloodstream by the kidneys. It follows from the above that ingesting creatine as a supplement to boost muscle stores inevitably results in higher levels of creatinine formation via creatine breakdown.

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The ‘satisfactory’ range of blood creatinine is 64-104micromols per litre (μmol/L), whereas my result of 110μmol/L was considered slightly above the satisfactory range. Given there were no other signs or symptoms indicating a compromised kidney function, no issue with another marker of kidney function (blood urea nitrogen [BUN]), nor any family history of such problems, my local physician ordered a repeat test to double check. That too came back slightly elevated at 106μmol/L. The physician was somewhat baffled but I suspected I knew the reason.

Mystery solved

Earlier in the year, I had decided to work hard on my base levels of strength. Having set up a gym in the garage, I had been following a rigorous strength program, which was of course supported by an optimum nutrition and recovery program (I do practice what I preach!). In addition to a somewhat increased protein intake and additional post-workout protein, I had also begun using creatine on a regular basis (2 grams per day), which I found subjectively at least, had helped maximize strength gains.

Following the blood results, I looked at the research on kidney function testing via blood creatinine measurement, and discovered that, although not widely appreciated in the medical community, athletes taking creatine supplements or on high-protein diets will almost certainly record higher than normal levels of blood creatinine but with completely normal kidney function (since the more creatine is ingested, the higher the rate of creatinine formation).

A good example of this is reported in the British Medical Journal, which reported on a case study of a lean and muscular, 42-year old male who regularly performed heavy-duty strength training and also took protein and creatine supplements⁽¹¹⁾. He had never used anabolic steroids but consumed a high-protein diet (consisting of daily chicken and white fish), and took regular ‘muscle enhancing’ supplements including creatine, collagen and protein. He had been taking creatine for four months, and used the supplement five times a week on training days.

While undergoing medical screening, routine blood testing revealed a serum creatinine of 198µmol/L. The blood test was repeated a week later and a serum creatinine level of 227 µmol/L was reported (over double the maximum level considered satisfactory). The patient was referred to a specialist renal clinic for further assessment. Because of concerns about his kidney health, this gentleman was then advised to discontinue all bodybuilding supplements as they could be aggravating what the clinicians suspected was a potentially serious condition.

Two weeks later at the follow-up specialist appointment, blood pressure, heart and lung sounds and examination of the abdomen were all normal, and there was no sign of any impairment of kidney function. Moreover, on his creatinine levels had returned to within normal range, at 104 µmol/L (see figure 2). The specialist concluded that the patient’s kidney function was completely normal and that the high creatinine levels recorded in initial testing were due to the consumption of creatine and a high protein intake.

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Figure 2: Blood creatinine levels⁽¹¹⁾

Two weeks after discontinuing creatine supplementation, creatinine levels fell back to within the normal range.

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More generally, research reports that the ingestion of creatine skewing kidney function test results in otherwise healthy fit individuals is an under recognized issue because the link between the consumption of such products and the blood results obtained can be easily overlooked during a physician consultation. Willis et al reported on a series of cases in which creatine supplementation was mistaken for kidney function impairment in patients who were HIV positive⁽¹²⁾. It was suspected that the patients were experiencing kidney insufficiency secondary to their condition or as a result of their antiretroviral therapy. It was eventually recognized that creatine supplements were responsible, because their creatinine levels fell back to within normal range at times when the supplements were not used due to periods of illness. At these times the patients abstained from using creatine as they were not able to attend the gym.

The literature also documents further reports of the erroneous misdiagnosis of kidney function following blood testing in athletes consuming higher than normal levels of protein and/or creatine⁽¹³⁾. Meanwhile, Velema and Ronde described a similar case as above in which creatine was responsible for elevated serum creatinine in the absence of kidney pathology⁽¹⁴⁾. It should also be noted that even where creatine is not supplemented, it is important to remember that high muscle mass alone independently correlates with high levels of serum creatinine⁽¹¹⁾. This is due to increased supply and turnover of creatine phosphate. Thus a very muscular athlete could record marginally above normal range levels of creatinine, even without any creatine ingestion.

Practical implications

If you’re an athlete who needs to undergo blood screening, or you have athletes in your care that do, you should be aware that kidney function tests can be skewed if creatine is consumed regularly, especially in athletes with high muscle mass and/or consuming a high-protein diet. Creatinine has a half-life of around of four hours, so you would expect creatinine levels to decay progressively once creatine ingestion is ceased. This explains in the case study above why serum creatinine had fallen to an acceptable value two weeks after the patient discontinued the supplements⁽¹¹⁾. However, it is also easy to imagine how these levels could build up over time through continued creatine use. It makes therefore that athletes needing to undergo blood tests that include kidney function should refrain from creatine supplementation and excessive protein intake for at least a week, and preferably two weeks prior to testing.

References

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