Kreatin og kræft – passer det?

For nogle år siden blev der udgivet en fransk rapport, der fremsatte en hypotese om øget risiko for kræft ved kreatinindtagelse. Denne hypotese blev dog hurtigt skudt i sænk af førende eksperter inden for området

Historien var i Politiken og andre aviser. Politiken havde sandsynligvis fået historien fra Ritzau, som igen har historien fra en meddelelse de franske sundhedsmyndigheder. Meddelelsen udspringer fra en længere rapport, som de franske myndigheder har fået udarbejdet omkring kreatins virkninger og bivirkninger.

Det tager lidt tid at komme igennem rapportens 54 sider (på fransk), men umiddelbart ser rapporten ud til at være noget subjektiv. Rapporten baserer sig ikke på nye franske undersøgelser, men tolker blot på allerede publicerede artikler. En væsentlig del af rapporten er faktisk baseret på et fremragende review på 107 sider publiceret i Physiological Reviews (se link længere nede på siden).

Kort fortalt baserer spekulationerne sig på to forhold:

1. I forbindelse med visse sygdomme bliver “kreatinstofskiftet” påvirket. Man argumenterer så lidt baglæns og siger: hvad nu hvis man påvirker “kreatinstofskiftet” – udløser man så de tilsvarende sygdomme?

2. Kreatin og kreatinin indgår i de kemiske processer, hvor der dannes kræftfremkaldende (carcinogene) stoffer, når visse madvarer steges eller grilles kraftigt.

Som vi umiddelbart tolker materialet, så er konklusionen følgende: De skadelige kemiske forbindelser, der kan skabes i laboratoriet ved høje temperaturer, forekommer med al sandsynlighed ikke i det menneskelige fordøjelsessystem. Groft sagt kan man sige, at så længe man ikke griller sit kreatinpulver sammen med en bøf, så er risikoen hypotetisk.

Det skal lige nævnes at to andre misforståelser har indsneget sig i Politikens historie:

1. Forskerne er IKKE uenige om kreatintilskuds præstationsfremmende egenskaber. Effekten varierer en del mellem forskellige individer, men den gennemsnitlige effekt er indiskutabel.

2. Når kreatin ikke er på dopinglisten, er det IKKE fordi, at det ikke kan spores. Det er fordi, man ikke har diskuteret sig endeligt frem til om alle præstationsfremmende (ufarlige) stoffer skal på listen.

Reference:

Review: Creatine and creatinine metabolism
Wyss M, Kaddurah-Daouk R
Physiol Rev 2000 Jul;80(3):1107-213

Tilføjelse:
Forskere tager afstand fra den franske rapport om kreatin og kræftrisiko

Flere og flere anerkendte forskere ytrer deres mishag med den franske rapport og mediernes sensationslyst. Kritikken er generelt i tråd med hvad Motion-online umiddelbart konkluderede. En af de mere anerkendte kreatin-forskere, Mark Tarnopolsky, sendte nedenstående besked til den hollandske sportsscience-diskussionsliste. Vi bringer den her, så vores læsere kan se, at vi ikke er ene om kritikken af de franske myndigheder. Desuden giver teksten flere detaljer og referencer og er i det hele taget kompetent og læseværdig (og på engelsk).

(Mark Tarnopolsky) To whom it may concern:

There has recently been a rash of misinformation that has been spread around the world that has arisen from a statement made by a Mr. ? Dr. ? Martin Hirsch for the French Agency of Medical Security for Food (AFSSA), claiming a link between creatine monohydrate supplementation and cancer.
This is not supported by the literature and it is unfortunate that medical misinformation can be spread throughout the world so rapidly. This agency claims to have reviewed the literature using nutritional experts (yet does not list them so we can judge their credentials), and the author has not published a single paper in a peer reviewed journal (at least none that have appeared in PubMed). I found the statement to be somewhat accurate in several areas (with the exception that it states that creatine increases muscle cell water (10 %) – this is high and it is more likely 3 – 4 %)).

The MAJOR problems come when they/?he tries to make a comment about the potential side effects: 1. approximate translation of the AFSSA statement on cancer “considering that creatine and creatinine under certain circumstances, particularly in the presence of simple sugars and elevated amino acids, could have carcinogenic effects based on preliminary experimental arguments in vitro and in vivo have been equivocal”. [I am not aware of any studies showing that creatine taken with sugar and amino acids is carcinogenic – especially when taken in physiological amounts – any compound, even amino acids may be carcinogenic in high doses (see MSDS label on leucine!)].

The real issue comes with the statement that “with the potentially carcinogenic effects…” – this is unfounded and certainly the jump to stating that epidemiological studies have shown a link is complete fabrication and misinformation. This sort of misinformation is as bad as the health care fraud that some folks claim regarding unproven agents. I do agree that we need to concern ourselves about impurities in creatine and any unregulated substances (ie. Problems previously with tryptophan and eosinophilic myositis) and I am all for creatine and other neutraceuticals being exposed to rigorous purity testing by federal agencies – I do know that most of the creatine for the neurology studies is exposed to careful testing for impurities and other chemical standards – Many of the large reputable companies in the US and Canada buy their creatine from high quality sources.

It then goes on to say that the effects of high levels of creatine ingestion has not been studied in the short or long term (yet they claim there have been epidemiological studies). They quote that there are epidemiological studies showing difficulties with digestion, muscle cramps and apparently cardiovascular problems (???????? – not sure where this comes from – there are in fact 2 studies in humans with congestive heart failure showing benefits to performance and studies in animals showing cardioprotective effects and we have shown that it does not affect blood pressure (Mihic, et al, Med Sci Sports Exerc, 2000)). There are other issues with this – firstly there have been no true epidemiological studies of creatine use and papers are suggesting from this article that epidemiological studies show a possible risk – THIS IS ABSOLUTELY INCORRECT.

In the final summary they state that supplementation with creatine constitutes a risk, but it has been insufficiently evaluated, particularly in the long-term. With the potentially carcinogenic effects, it would be necessary for the regular reevaluation of studies.

I am shocked that this amount of misinformation can be placed on the internet by such and agency claiming legitimacy and trying to advocate for the good of people. This type of speculative misinformation does not serve the interests of anyone. Our group and others are carefully evaluating the risks and benefits of creatine monohydrate ingestion in patients with neuromuscular and neurometabolic disorders as well as in human aging – Patients reading this stuff in the papers have already called to drop out of studies. Creatine may be very helpful in a number of medical conditions and thanks to this inaccurate statement we will all have difficulty in recruiting and retaining subjects. Unfortunately, it is very difficult for the lay public to evaluate the quality of the information and the AFSSA statement violates many of the key factors to look for in judging legitimacy:

1. The person signing their name to the statement does not list their credentials.
2. The supposed scientists who evaluated the literature are not listed.
3. There is no evidence of external review of the statement.
4. The statement has internal inconsistencies (medium and long term studies
not done and yet concludes that epidemiological studies show their may be a
cancer risk).
5. There are no references to peer reviewed studies to support the
statement.

THERE ARE NO STUDIES IN HUMANS EVEN SUGGESTING AN INCREASED RISK OF CANCER
WITH CREATINE.

There are many papers showing an anti-cancer effect of creatine in animals:

Jeong KS, Park SJ, Lee CS, Kim TW, Kim SH, Ryu SY,
Williams BH, Veech RL, Lee YS. Effects of cyclocreatine in rat hepatocarcinogenesis model.
Anticancer Res 2000 May-Jun;20(3A):1627-33

Kristensen CA, Askenasy N, Jain RK, Koretsky AP.
Creatine and cyclocreatine treatment of human colon adenocarcinoma xenografts: 31P and 1H magnetic resonance spectroscopic studies.
Br J Cancer 1999 Jan;79(2):278-85

Schiffenbauer YS, Meir G, Cohn M, Neeman M.
Cyclocreatine transport and cytotoxicity in rat glioma and human ovarian carcinoma cells: 31P-NMR spectroscopy.
Am J Physiol 1996 Jan;270(1 Pt 1):C160-9

Ara G, Gravelin LM, Kaddurah-Daouk R, Teicher BA
Antitumor activity of creatine analogs produced by alterations in pancreatic hormones and glucose metabolism.
In Vivo 1998 Mar-Apr;12(2):223-31

Miller EE, Evans AE, Cohn M.
Inhibition of rate of tumor growth by creatine and cyclocreatine.Proc Natl Acad Sci U S A 1993 Apr 15;90(8):3304-8

There are several reviews of creatine so people can get their facts
straight:
Casey A, Greenhaff PL
Does dietary creatine supplementation play a role in skeletal muscle metabolism and performance?
Am J Clin Nutr 2000 Aug;72(2 Suppl):607S-17S

Tarnopolsky MA
Potential benefits of creatine monohydrate supplementation in the elderly.
Curr Opin Clin Nutr Metab Care 2000 Nov;3(6):497-502

Terjung RL, Clarkson P, Eichner ER, Greenhaff PL, Hespel PJ, Israel RG,
Kraemer WJ, Meyer RA, Spriet LL, Tarnopolsky MA, Wagenmakers AJ, Williams MH
American College of Sports Medicine roundtable. The physiological and health effects of oral creatine supplementation. Med Sci Sports Exerc 2000
Mar;32(3):706-17

Wyss M, Kaddurah-Daouk R.
Creatine and creatinine metabolism.
Physiol Rev 2000 Jul;80(3):1107-213

There are several reviews of safety:
Poortmans JR, Francaux M
Adverse effects of creatine supplementation: fact or fiction?
Sports Med 2000 Sep;30(3):155-70

Mihic S, MacDonald JR, McKenzie S, Tarnopolsky MA.
Acute creatine loading increases fat-free mass, but does not affect blood pressure, plasma
creatinine, or CK activity in men and women.
Med Sci Sports Exerc. 2000 Feb;32(2):291-6.

Terjung RL, Clarkson P, Eichner ER, Greenhaff PL, Hespel PJ, Israel RG, Kraemer WJ, Meyer RA, Spriet LL, Tarnopolsky MA, Wagenmakers AJ, Williams MH
American College of Sports Medicine roundtable. The physiological and health effects of oral creatine supplementation.
Med Sci Sports Exerc 2000 Mar;32(3):706-17

I would hope that Reuters, ESPN, National Post, Associated Press, etc. would get their facts straight before they put out misinformation. I know that a flashy inflammatory and inaccurate statement is better for press, but please think of the patients who are involved in the studies and those who may stand to benefit from carefully controlled evaluation of the risks and benefits of creatine supplementation. Yes, there may be some side effects, but please, let the researchers evaluate what these are and the incidence so that people can evaluate the risks and benefits of supplementation in an unbiased manner.

Sincerely,
Mark Tarnopolsky, MD, PhD, FRCP(C),
Neuromuscular Disease Unit, 4U4 Neurology,
McMaster University Medical Center,
Hamilton, Ontario, CANADA, L8N 3Z5
1-905-521-2100 (x75226/76593).
FAX 905-521-2656.
[email protected]