C Pharmacology & Toxicology 2003, 93, 153–155. Copyright CPrinted in Denmark . All rights reserved

ISSN 0901-9928

Annotations & Reflections

Should Aspirin be Used to Counteract‘Salicylate Deficiency’?

Gareth Morgan

National Public Health Service for Wales, 36 Orchard Street, Swansea, U.K. SA1 5AQ

(Received June 23, 2003; Accepted August 12, 2003

Abstract: Aspirin (acetylsalicylate) is an inexpensive drug that is used extensively to reduce cardiovascular disease risk.Emerging evidence suggests that aspirin reduces the risk of other chronic diseases such as certain forms of cancer. Salicyl-ate may contribute to the disease reduction effects. It is present naturally in fruits and vegetables and individuals with alow intake of these foods may be ‘salicylate deficient’. This deleterious state may constitute a significant public healththreat. Interventions to prevent deficiency, such as low-dose aspirin programmes, could have substantial beneficial healthimpacts around the world.

Aspirin (acetylsalicylate) is an inexpensive and widely useddrug. It can exert undesirable effects such as gastrointestinalirritation but low-dose aspirin (e.g. 75 mg per day) is rela-tively safe (Serrano et al. 2002). It is used extensively toreduce cardiovascular disease morbidity and mortality risksin individuals predisposed to myocardial infarction andischaemic stroke (Antithrombotic Trialists’ Collaboration2002; Hayden et al. 2002; van Walraven et al. 2002; Weis-man & Graham 2002). This effect has been attributed toacetylation of platelet cyclooxygenase leading to reducedthromboxane production.

Emerging evidence suggests that the regular use of as-pirin results in a reduced risk to develop certain chronicdiseases such as certain forms of cancer and possibly Alzh-eimer’s disease (Bossetti et al. 2002; Zandi et al. 2002;Corley et al. 2003; Muscat et al. 2003). Aspirin thereforemay offer far-reaching public health benefits and couldmake a substantial beneficial impact to disease reductionprogrammes (Vainio et al. 2002; Morgan 2003a & b). Theaspirin metabolite salicylate has antioxidant, antiinflam-matory and proapoptotic properties (Amano & Peskar2002; Thun et al. 2002) which may contribute to the diseasereduction effects.

Salicylates are widely produced by fruits, vegetables andother plant species. Individuals who consume largeamounts of fruits and vegetables have blood salicylate levelssimilar to individuals taking low-dose aspirin (Blacklock etal. 2001). It has been suggested that salicylate may contrib-ute, at least in part, to the health promoting properties of

Author for correspondence: Gareth Morgan, Department of PublicHealth, National Public Health Service for Wales, 36 OrchardStreet, Swansea SA1 5AQ, U.K. (fax π44 1792 607533, e-mailgareth.morgan/nphs.wales.nhs.uk).

fruits and vegetables (Paterson & Lawrence 2001; Scheier2001). Conceivably, the discrepancy between observationalstudies showing health promoting effects of fruits and veg-etables and randomised intervention trials of vitaminsupplements that show no beneficial effect (Davey-Smith &Ebrahim 2003) might be partly explained by salicylate infood. Given the properties of salicylate this is biologicallyplausible since long-term inflammation appears to set thestage for the development of chronic diseases such as car-diovascular disease, cancer and Alzheimer’s disease (Cous-sens & Werb 2002; Libby 2002).

The evidence suggests that the intake of salicylate(whether in food or in drugs) may be beneficial to healthand associated with a reduced risk to develop certainchronic diseases. It follows that ‘salicylate deficiency’ couldbe deleterious to health (fig. 1) and that it may developbecause of a low intake of fresh fruits and vegetables. Thereis also a related issue of food production. In fruits and veg-etables, salicylate-mediated apoptosis contributes to de-fence mechanisms against damage and disease. This maypartly explain why vegetables grown in natural conditionsappear to have a higher content of salicylate than thosegrown in more controlled conditions (Baxter et al. 2001).Therefore, the ‘Western’ lifestyle of high fat intake and lowintake of fruits and vegetables (that contain reduced salicyl-ate levels) is likely to result in ‘salicylate deficiency’.

In certain situations, therefore, aspirin may be used totreat (or counteract) ‘salicylate deficiency’. For example, theuse of aspirin in individuals at high risk of cardiovasculardisease events needs to be increased (Carroll et al. 2003)and because of lifestyle factors many high-risk individualswill be predisposed to ‘salicylate deficiency’. Therefore, theuse of aspirin should be considered as a complement not acompetitor to other disease reduction methods such as life-

154 GARETH MORGAN Annotations & Reflections

Fig. 1. A hypothetical scheme of potential connections between inflammation, salicylate and chronic disease risk.

155ASPIRIN AND ‘‘SALICYLATE DEFICIENCY’’Annotations & Reflections

style change. However, in ‘salicylate-deficient’ individualsthat resist lifestyle changes low-dose aspirin may be an ef-fective and appropriate intervention strategy to reduce therisk of chronic disease. The decision to use aspirin must bebased on a clinical judgement that the benefits will outweighthe harms (Loke et al. 2003).

‘Salicylate deficiency’ may constitute a significant publichealth threat and further research is required given thatlittle is known about it. Possible avenues to be consideredinclude the potential of targeted ‘salicylate deficiency’screening programmes (e.g. using bioassay methods) to pre-dict chronic disease risk and public health interventions toprevent deficiency. The latter could include lifestyle changes,low-dose aspirin programmes, fortification of food anddrinking water with synthetic salicylate and changes of foodproduction methods. The proper targeting of these inter-ventions could have substantial beneficial impacts aroundthe world and help to reduce health inequalities. Therefore,future international scientific meetings on aspirin (Morgan2003b) should also consider the intimately linked issue of‘salicylate deficiency’.

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