Salicylic acid: are we already taking aspirin?

Salicylic acid has a long history of use in medicine. Nowadays it’s a common ingredient in many skincare products and central component of the anti-inflammatory drugs aspirin (acetylsalicylic acid, ASA) and mesalazine (5-aminosalicylic acid, 5-ASA). Major pharmacological targets of salicylic acid include inhibition of COX (inflammation) and activation of AMPK (energy homeostasis).

Perhaps less well known, is that salicylic acid is a natural phenolic molecule widely distributed throughout nature. Salicylic acid is present in many plants; the name derives from the willow tree (Latin Salix) where it was originally obtained. Low levels of salicylic acid are also already present in the blood of animals, both carnivores and herbivores, some of which may come from internal biosynthesis and the rest from diet ¹.

Significant levels of salicylic acid, and its immediate precursor benzoic acid, are present in many plant foods (e.g. fruit, veg, herbs and spices) ^2,3. In humans, fruit and veg consumption increases salicylic acid in blood ². The highest levels have been reported in western vegetarians and rural Indians, with levels that overlap with chronic low-dose aspirin use (75mg/day) ^1,4. Salicylic acid might therefore be a bioactive phytochemical mediating some benefits of plant foods ^2,5,6.

Gut microbes could also potentially be a source of salicylic acid. Some preliminary studies on germ-free animals seemed to rule out the gut microbiota as a source of blood levels ¹. However recently a metabolic screening identified salicylic acid as a key metabolite mediating the anti-inflammatory activity of the probiotic bacterium Faecalibacterium prausnitzii ⁷. In healthy humans, F. prausnitzii is one of the most abundant bacteria in the gut (>5% of the microbiota), whereas low levels have consistently been reported in inflammatory bowel disease (IBD), and also recently psoriasis ⁸. Therefore colonic levels of salicylic acid may also be low in these conditions, whereas the salicylate drug mesalazine is used to reduce inflammation and induce remission in IBD.

References

1.         Paterson, J. R. et al. Salicylic acid sans aspirin in animals and man: persistence in fasting and biosynthesis from benzoic acid. J. Agric. Food Chem. 56, 11648–52 (2008).

2.         Rinelli, S. et al. Circulating salicylic acid and metabolic and inflammatory responses after fruit ingestion. Plant Foods Hum. Nutr. 67, 100–4 (2012).

3.         Aresta, A. & Zambonin, C. Simultaneous determination of salicylic, 3-methyl salicylic, 4-methyl salicylic, acetylsalicylic and benzoic acids in fruit, vegetables and derived beverages by SPME-LC-UV/DAD. J. Pharm. Biomed. Anal. 121, 63–8 (2016).

4.         Paterson, J. R., Srivastava, R., Baxter, G. J., Graham, A. B. & Lawrence, J. R. Salicylic acid content of spices and its implications. J. Agric. Food Chem. 54, 2891–6 (2006).

5.         Duthie, G. G. & Wood, A. D. Natural salicylates: foods, functions and disease prevention. Food Funct. 2, 515–20 (2011).

6.         Pomponi, M. & Pomponi, M. F. L. Alzheimer’s disease prevention & acetyl salicylic acid: a believable story. Indian J. Med. Res. 139, 1–3 (2014).

7.         Miquel, S. et al. Identification of metabolic signatures linked to anti-inflammatory effects of Faecalibacterium prausnitzii. MBio 6, (2015).

8.         Eppinga, H. et al. Similar depletion of protective Faecalibacterium prausnitzii in psoriasis and Inflammatory Bowel Disease, but not in Hidradenitis Suppurativa. J. Crohns. Colitis (2016). doi:10.1093/ecco-jcc/jjw070