Study: Is creatine dangerous?

Geschatte leestijd: 7 minuten Long-term use of creatine poses no risk to the kidneys. Various studies have been conducted in this area that have unanimously shown that long-term use of creatine monohydrate poses no risk.

No Long-Term Effects on Kidneys

This week I wrote an article about the effect of high protein intake on the kidneys. The kidneys have a filtering function, and high protein intake would supposedly burden them more (but in practice, this turns out to be not much of an issue). Similar concerns are also raised about the long-term intake of creatine. Creatine, which is consumed in the muscles as fuel, leads to the breakdown product creatinine. This breakdown product, which ends up in the blood, needs to be removed by the kidneys and then excreted in the urine. More creatine leads to more creatinine that needs to be processed by the kidneys, potentially causing excessive strain. Considerable research has been conducted in this area over the past 15 years, and for a change, it all leads to the same conclusion: Long-term creatine use does not result in adverse effects on the kidneys. This makes my work here much easier. Normally, I not only have to research and explain all relevant sources, but also often clarify the differences. Because there seems to be agreement here, I can let the studies speak for themselves. Take, for example, the research from the Free University of Brussels in 1999 [1]. Nine young athletes received creatine for 10 months to five years, and this did not result in any side effects on the kidneys:

Neither short-term, medium-term, nor long-term oral creatine supplements induce detrimental effects on the kidney of healthy individuals. – J.R. Poortmans, Université Libre de Bruxelles

The only thing that is unclear to me about this study is the choice of dosage. At least, there seems to be no choice made except for an absolute minimum and maximum. They received 1 to 4 ker per day 1 to 20 grams of creatine. That is a range of 1 to 80 grams per day, leaving a lot of questions open about the so-called dose-dependent effect – to what extent are potential effects dependent on the dosage? It is particularly difficult because we want to see the effects of at least 5 grams per day since this is what most people take during the “maintenance phase”. In this study, there may be people who only took 1 gram daily. In a study from Truman State University in 2002, different dosages were also used, but fortunately at least 5 grams per day [2]. Twenty-three trained college football players received 5 to 20 grams of creatine per day for a minimum of 3 months to a maximum of five and a half years. They also found no adverse effects on the kidneys (and liver).

Therefore, it appears that oral supplementation with CrM has no long-term detrimental effects on kidney or liver functions in highly trained college athletes in the absence of other nutritional supplements. -D.L. Mayhew, Truman State University

American football players seem to be popular guinea pigs because a year later, 98 of them received an average of 5 grams of creatine per day for 21 months (after a loading period of one week with 15.75 grams per day)[3]. Once again, the researchers did not observe any adverse effects on, among other things, the kidneys.

Results indicate that long-term creatine supplementation (up to 21-months) does not appear to adversely affect markers of health status in athletes undergoing intense training in comparison to athletes who do not take creatine. -R.B. Kreider, University of Memphis

All of these studies were conducted among young athletes. This is indeed an interesting group because as athletes, they are more likely to use such supplements than non-athletes. However, creatine is also used in certain medical conditions to increase muscle mass. German researchers therefore looked at the long-term effect of creatine on the kidneys in older individuals with Parkinson’s [4]. Sixty patients received either a placebo or 4 grams of creatine per day for two years. After two years, the researchers found that there was more creatinine in the urine of the people who had received creatine. This is not strange because more creatine inevitably leads to more creatinine. However, the increase in creatinine had no adverse effect, as other important values measured in the kidneys remained normal.

Although serum creatinine levels increased in Cr patients because of the degradation of Cr, all other markers of tubular or glomerular renal function, especially cystatin C, remained normal, indicating unaltered kidney function. The data in this trial provide a thorough analysis and give a detailed overview about the safety profile of Cr in older age patients. A. Bender, University of Munich-Klinikum

Dangerous with Impaired Glomerular Filtration Rate (GFR)

Just like with protein intake, people who already have impaired kidney function may experience additional symptoms. However, this is only a (logical) assumption that has not yet been proven in research [5].

The studies completed to date suggest that in normal healthy individuals the kidneys are able to excrete creatine, and its end product creatinine, in a manner that does not adversely alter renal function. This situation would be predicted to be different in persons with impaired glomerular filtration or inherent renal disease. -W.B. Farquhar, Harvard Division on Aging

Creatine Itself Safe, but Possible Risks Due to Contamination – Sole Side Effect: Increase in Lean Mass

In healthy individuals, however, there are no risks to the kidneys. It is important to realize that all these studies focus on creatine as a product. This does not mean that the creatine you receive in a jar may not pose risks. I have previously written about supplements deliberately “contaminated” to make them more effective. Think of (meth)amphetamine in fat burners, but also the Dutch footballers (Davids, Jaap Stam, Frank de Boer, Van Nistelrooy) who were suspended for doping use because, according to them, nandrolone (an anabolic steroid) was found in their creatine. In addition to deliberate contamination, there is also the risk of unintentional contamination or contamination due to negligence during the production process.

Furthermore, a possibly unexpected outcome related to creatine monohydrate ingestion is the amount of contaminants present that may be generated during the industrial production. Recently, controlled studies made to integrate the existing knowledge based on anecdotal reports on the side effects of creatine have indicated that, in healthy subjects, oral supplementation with creatine, even with long-term dosage, may be considered an effective and safe ergogenic aid. E. Bizzarini, University of Trieste

Although these researchers warn of possible contamination during the production process, their main conclusion is that long-term creatine use can be considered safe by itself [6]. Personally, I am therefore a fan of CreaPure creatine, known for its high quality and rigorous production process. Moreover, nowadays, you unfortunately have to worry about more production processes than just that of creatine. For example, consider the ladies of the Chinese volleyball team who were not allowed to eat meat in preparation for the 2012 Olympic Games due to fears of contamination with clenbuterol. This performance-enhancing drug is banned by WADA (World Anti-Doping Agency), but is sometimes given to Chinese farmers to accelerate the growth of their livestock. But well, China happens to be the country that, as a producer of creatine, is not exactly known for its good quality.

What Are the Long-Term Side Effects of Creatine Use?

Although safe for the kidneys (and liver) of healthy individuals, there may be some side effects. However, these are less serious than kidney or liver problems would be. Bizzarini’s research even mentions a positive side effect [6]. The only side effect they mention is an increase in lean mass! However, I cannot call this a side effect because for most people, this is precisely the effect of creatine (along with increased strength) and not a side effect. However, if you are a endurance athlete focusing on strength, for example, then this is not what you want, but creatine is not suitable for endurance sports anyway.

Nausea and Diarrhea from Creatine

Although the saying goes that you have never really trained if you have never vomited in the gym, I can tell you from experience that this is not really desirable. Apart from the fact that nausea beforehand prevents you from going all out, you feel extremely disappointed if you have managed to finish your workout, but then see your post-workout shake leave your stomach faster than it entered. After all, that’s a waste of protein and creatine! Even if you manage to keep it in a little longer, but it flies out the other end a bit later, you often don’t feel happier. Researchers from Utrecht saw a possible risk here, but it turns out to be very limited [7]. They gave 10 grams of creatine per day to the subjects, who were on average 57 years old, for 310 days. In terms of numbers, they saw hardly any difference between people who received creatine and the placebo group. Nausea was similar, as were stomach complaints, but diarrhea occurred more frequently in the creatine group, as did edema in the limbs due to fluid retention (which may also be related to age). However, it is striking that in some cases, nausea in the creatine group disappeared when creatine was stopped. Although there was just as much nausea in the creatine group as in the placebo group, it seems that (at least in those few more severe cases) creatine was the cause. It is good to know why this group was chosen. They were all people suffering from Amyotrophic Lateral Sclerosis (ALS). Creatine may have a protective effect in this neurological disease. However, muscle cramps are one of the symptoms of this condition, so I do not know to what extent these exacerbate the effects of creatine on the stomach.

Creatine Monohydrate or “Special Creatine”

All the studies mentioned above were conducted using creatine monohydrate. Creatine is now offered in many different forms. Think of creatine ethyl ester (malate), micronized creatine, creatine serum, creatine citrate, etc. The effects of all these different types of creatine have hardly been studied (in independent research). Let alone that the long-term effects have been studied. Therefore, little can be said about the safety and effectiveness of these. Personally, I mainly see in all these different forms attempts by manufacturers to earn something from creatine, of which the monohydrate form is cheap and sold by almost everyone. By offering “special” supposedly better forms, they hope to distinguish themselves from the competition and charge a higher price. Therefore, I stick with creatine monohydrate and advise you to do the same.

Summary

• Long-term use of creatine seems to have no adverse effects on healthy individuals. The research on this topic surprisingly shows unanimous agreement.
• There may be a risk for people already suffering from kidney problems.
• Consideration should be given to possible contamination. However, this is not a risk of creatine itself but of the production process. This can be taken into account by choosing certain producers who guarantee quality.
• The only side effects observed in studies were slightly more cases of nausea among older participants with ALS.
• The safety studies were conducted with creatine monohydrate and therefore say nothing about other types of creatine.

References

1. Poortmans JR, Francaux M. Long-term oral creatine supplementation does not impair renal function in healthy athletes. Med Sci Sports Exerc. 1999 Aug;31(8):1108-10. PubMed PMID: 10449011.
2. Mayhew DL, Mayhew JL, Ware JS. Effects of long-term creatine supplementation on liver and kidney functions in American college football players. Int J Sport Nutr Exerc Metab. 2002 Dec;12(4):453-60. PubMed PMID: 12500988.
3. Kreider RB, Melton C, Rasmussen CJ, Greenwood M, Lancaster S, Cantler EC, Milnor P, Almada AL. Long-term creatine supplementation does not significantly affect clinical markers of health in athletes. Mol Cell Biochem. 2003 Feb;244(1-2):95-104. PubMed PMID: 12701816.
4. Bender A, Samtleben W, Elstner M, Klopstock T. Long-term creatine supplementation is safe in aged patients with Parkinson disease. Nutr Res. 2008 Mar;28(3):172-8. doi: 10.1016/j.nutres.2008.01.001. PubMed PMID: 19083405.
5. Farquhar WB, Zambraski EJ. Effects of creatine use on the athlete’s kidney. Curr Sports Med Rep. 2002 Apr;1(2):103-6. Review. PubMed PMID: 12831718.
6. Bizzarini E, De Angelis L. Is the use of oral creatine supplementation safe? J Sports Med Phys Fitness. 2004 Dec;44(4):411-6. Review. PubMed PMID: 15758854.
7. 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 May;26(4):307-13. PubMed PMID: 15795816.