Tuesday, 7 June 2011

Luca Mascitelli role of Aspirin in reducing Iron, Cancer effect, 14 May 2011, The Lancet

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Luca Mascitelli, Mark R Goldstein
Peter Rothwell and colleagues 1 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-infl ammatory drugs had no signifi cant effect on serum ferritin concentrations.

A protective effect of iron loss on cancer mortality was confi rmed in a randomised trial in which patients were randomly assigned to reduction in iron stores by calibrated phlebo tomies or to observation. Over 4·5 years, the risk of new cancers was signifi cantly lower in the iron reduction group than in controls.4 Furthermore, in patients with new cancers, those with iron reduction had highly signifi cantly lower cancerspecifi c 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 eff ects 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 confl icts of interest. *Luca Mascitelli, Mark R Goldstein Medical Service, Comando Brigata alpina “Julia”, Via S Agostino 8, 33100 Udine, Italy (LM); and Fountain Medical Court, Bonita Springs, FL, USA (MRG)

1 Rothwell PM, Fowkes FG, Belch JF, Ogawa H, Warlow CP, Meade TW. Eff ect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. Lancet 2011; 377: 31–41.
2 Mascitelli L, Pezzetta F, Sullivan JL. Aspirin-associated iron loss as an anticancer mechanism. Med Hypotheses 2010; 74: 78–80.
3 Milman N, Ovesen L, Byg K, Graudal N. Iron status in Danes updated 1994, I: prevalence of iron defi ciency and iron overload in 1332 men aged 40-70 years. Infl uence of blood donation, alcohol intake, and iron supplementation. Ann Hematol 1999; 78: 393–400.
4 Zacharski LR, Chow BK, Howes PS, et al. Decreased cancer risk after iron reduction in patients with peripheral arterial disease: results from a randomized trial. J Natl Cancer Inst 2008; 100: 996–1002.
5 Mascitelli L, Goldstein MR. Inhibition of iron absorption by polyphenols as an anti-cancer mechanism. QJM 2011; 104: 459–61.

Peter Rothwell Reply
Luca Mascitelli and Mark Goldstein raise the issue of the possible eff ect 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 insuffi cient 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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