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DOI: 10.1055/s-2001-16662
© Georg Thieme Verlag Stuttgart · New York
Kalzium und Antioxidanzien als Supplemente in der Krebsprophylaxe - Statusbericht zu den Interventionsstudien
Calcium and Antioxidants as Supplements in Cancer Prophylaxis - Status Report on Interventional StudiesPublikationsverlauf
Publikationsdatum:
27. August 2001 (online)

Zusammenfassung
Ein wichtiger Baustein zur Evidenz, die den Einsatz von Ernährungssubstanzen in der Krebsprophylaxe nahe legt, sind doppelblind angelegte randomisierte lnterventionsstudien, die eine Risikosenkung beim Einsatz der zu untersuchenden Substanz im Vergleich zu einer Plazebosubstanz an dem Zielkrankheitsbild, hier Krebserkrankung, nachweisen. Gleichzeitig können diese Studien zusätzlich den Nachweis erbringen, dass das Risiko für andere Krankheitsbilder nicht erhöht ist. Im Rahmen der Primärprophylaxe gibt es neben vier größeren abgeschlossenen lnterventionsstudien mit 20 000 bis 30 000 Personen eine Reihe von kleineren Studien in der Größenordnung von 500 bis 3000 Personen, die potenzielle krebsprophylaktische Substanzen aus dem Ernährungsbereich an Hochrisikogruppen überprüft haben. In diesen Studien wurden Vitamin A, β-Karotin, Vitamin E, Selen und Kalzium entweder als Reinsubstanz eingesetzt oder in unterschiedlichen Kombinationen, zum Teil auch mit anderen Substanzen. Im Bereich des Einsatzes von Reinsubstanzen besaß bis auf Kalzium keine der Substanzen in Bezug auf die Primärhypothese eine risikoreduzierende Wirkung. Kalzium reduzierte die Rekurrenz von Darmpolypen. Dieses Modell lässt jedoch nur bedingt Rückschlüsse auf das Kolonkrebsrisiko zu. Auch im Bereich der überprüften Sekundärhypothesen gab es viele „Null”-Ergebnisse zur Gesamtkrebsmortalität und einzelnen Krebsformen. Bemerkenswerte Supplementierungseffekte konnten bei Selen und Vitamin E für spezielle Krebserkrankungen beobachtet werden. Bei Selen wurden in einer kleineren lnterventionsstudie risikosenkende Effekte für die Gesamtkrebsmortalität und speziell für Lungen-, Prostata- und Kolonkrebs beobachtet. Die Supplementierung von Vitamin E ergab eine Absenkung des Prostatakarzinomrisikos. Gleichzeitig hat diese Studie ergeben, dass in der Vitamin-E-Supplementierungsgruppe das Risiko für einen hämorrhagischen Schlaganfall angestiegen ist. Beide Ergebnisse bedürfen vor weiteren Schlussfolgerungen der Überprüfung. β-Karotin ist die Substanz, die am häufigsten in lnterventionsstudien zur Anwendung kam. Hier konnte festgestellt werden, dass bei Risikogruppen wie Rauchern das Krebsrisiko ansteigt und in der nichtrauchenden Bevölkerung keine Effekte auf das Krebsrisiko bei einer Supplementierung durch β-Karotin zu beobachten waren. Eine lnterventionsstudie in Kolumbien erbrachte Hinweise, dass β-Karotin und Vitamin C präkanzeröse Läsionen im Magen verstärkt zur Abheilung bringen können und so möglicherweise das Magenkrebsrisiko verringern. Als Fazit ergibt sich, dass aus den lnterventionsstudien für viele Einzelsubstanzen der Nachweis besteht, dass sie nicht krebsprophylaktisch wirken und bei einigen der Hinweis, dass der (Zufalls-)Befund einer organspezifischen Krebsrisikosenkung zunächst auf eine solide Basis gestellt werden muss.
Calcium and Antioxidants as Supplements in Cancer Prophylaxis - Status Report on Interventional Studies
The evaluation of the use of single substances for cancer risk reduction should base on the review of total evidence which should show unequivocal inference of its effectiveness. An important part of the generation of evidence are double-blind randomised intervention studies which demonstrate a reduction in risk in connection with the substance of investigation compared to a placebo substance in correlation to a certain disease, cancer. Such studies can also show i.e., in this case, that the risk for other diseases is not increased. In cancer research antioxidative substances had been preferentially investigated regarding their risk-reducing properties. In the area of primary prevention the number of successfully completed double-blind randomised intervention studies with cancer as endpoint or surrogate endpoint near to cancer such as the recurrence of colon polyps is still limited. Aside from larger intervention studies with 20 000 to 30 000 study participants there are a number of smaller studies 500 to 3000 subjects in size which tested potentially cancer risk reductive substances in high-risk groups. Intervention studies with smaller numbers were not considered in this review due to problems with the statistical significance and in addition such studies with surrogate endpoints which had been far away from the actual tumour. Test substances had been in particular vitamin A, β-carotene, vitamin E, selenium, and calcium. These substances were applied either as pure substances or in different combinations. For each intervention study first a primary hypothesis was formulated and subsequently various secondary hypotheses, if at all, in the course of the study. With the exception of calcium none of the substances showed risk-reducing effects in relation to the primary hypothesis. Calcium was applied in the model of colon polyp recurrence that however, allows only limited reference to the risk of colon cancer. Interesting results in the area of the secondary hypothesis were found in relation to selenium and vitamin E. Risk-reducing effects were observed for lung, prostate and colon cancer in a small intervention study with selenium. This result requires further testing because the study design is not well suited in the area of primary prevention and due to the small numbers observed a further test in a larger study taking the normal population might be useful. The supplementation of vitamin E resulted in reduction in risk for prostate cancer in a large intervention study with vitamin E. This result, too, should be re-tested. This study also showed that the risk of haemorrhagic stroke was increased in the group with vitamin E supplementation. β-carotene is a substance which has been most tested in intervention studies. For this substance it could be revealed that particular risk groups such as smokers exhibit an increased lung cancer risk and in the non-smoking population no effect on risk had been observed by supplementation with β-carotene. An intervention study in Columbia observed that β-carotene and vitamin C support regression of pre-cancerous lesions in the stomach and may in this way contribute to reduce the risk of gastric cancer. lt can be concluded from the intervention studies that for many dietary substances evidence exists that they do not reduce the risk of cancer and for some of them that the result of an organ-specific reduction in risk needs to be put on a solid basis.
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Dr. Heiner Boeing
Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke
Abteilung Epidemiologie
Arthur-Scheunert-Allee 114 - 116
14558 Bergholz-Rehbrücke
eMail: boeing@www.dife.de