Monday, 30 January 2012

Iron loss as mechanism for reduction of cancer deaths with aspirin

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The Lancet, Volume 377, Issue 9778, Page 1650, 14 May 2011
doi:10.1016/S0140-6736(11)60667-3Cite or Link Using DOI

Aspirin in the prevention of cancer

Peter Rothwell and colleagues1 provide new evidence that long-term daily aspirin lowers mortality from several common cancers. However, the mechanisms underlying this beneficial effect are not clearly understood. A plausible anti-tumour mechanism of long-term aspirin use that was not considered is aspirin-mediated chronic iron loss, as previously suggested.2
Loss of stored iron is known to be possible even in aspirin users with clinically undetectable occult gastric bleeding. Indeed, long-term aspirin use has been shown to be associated with roughly 20% lower serum ferritin concentrations—a good indicator of body iron stores—than in non-users;3 treatment with other non-steroidal anti-inflammatory drugs had no significant effect on serum ferritin concentrations.
A protective effect of iron loss on cancer mortality was confirmed in a randomised trial in which patients were randomly assigned to reduction in iron stores by calibrated phlebotomies or to observation. Over 4·5 years, the risk of new cancers was significantly lower in the iron reduction group than in controls.4 Furthermore, in patients with new cancers, those with iron reduction had highly significantly lower cancer-specific and all-cause mortality than controls. These findings are plausible in view of the growing number of published studies on the role of iron in carcinogenesis.2
In this setting, we have also proposed that lower stored iron concentrations mediated by inhibition of iron absorption by polyphenols present in the diet might exert an anti-cancer mechanism.5
Future studies of aspirin action should therefore include assessment of the effects of the intervention on iron status. If iron loss is found to be a mechanism, this consequence of aspirin use can be clinically replicated by other methods without incurring the risk of major aspirin-induced haemorrhage.2
We declare that we have no conflicts of interest.


1 Rothwell PMFowkes FGBelch JFOgawa HWarlow CPMeade TWEffect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trialsLancet 201137731-41Summary | Full Text | PDF(502KB) |CrossRef | PubMed
2 Mascitelli LPezzetta FSullivan JLAspirin-associated iron loss as an anticancer mechanismMed Hypotheses 20107478-80.CrossRef | PubMed
3 Milman NOvesen LByg KGraudal NIron status in Danes updated 1994, I: prevalence of iron deficiency and iron overload in 1332 men aged 40-70 years. Influence of blood donation, alcohol intake, and iron supplementationAnn Hematol 199978393-400CrossRef | PubMed
4 Zacharski LRChow BKHowes PS, et alDecreased cancer risk after iron reduction in patients with peripheral arterial disease: results from a randomized trialJ Natl Cancer Inst 2008100996-1002CrossRef | PubMed
5 Mascitelli LGoldstein MRInhibition of iron absorption by polyphenols as an anti-cancer mechanismQJM 2011104459-461.CrossRef | PubMed
a Medical Service, Comando Brigata alpina “Julia”, Via S Agostino 8, 33100 Udine, Italy
b Fountain Medical Court, Bonita Springs, FL, USA

Luca Mascitelli and Mark Goldstein raise the issue of the possible effect of aspirin treatment on iron loss as a mechanism for the reduction in cancer deaths. We deliberately did not review the many suggested mechanisms by which aspirin might reduce the risk of death due to cancer, but it is possible that reduced iron stores might contribute. There are currently insufficient data on the associations between iron stores and cancer risk to determine whether their pattern closely mirrors that of the effects of aspirin on deaths due to the specific cancers that we noted.

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