Low-Dose Aspirin Affects the Small Bowel Mucosa: Results of a Pilot Study With a Multidimensional Assessment

Published:December 29, 2008DOI:

      Background & Aims

      Whether low-dose aspirin (acetylsalicylic acid [ASA]) produces intestinal damage is controversial. Our aim was to determine whether the small bowel is damaged by low-dose ASA on a short-term basis.


      Twenty healthy volunteers (age range, 19–64 years) underwent video capsule endoscopy (VCE), fecal calprotectin, and permeability tests (sucrose and lactulose/mannitol [lac/man] ratio) before and after ingestion of 100 mg of enteric-coated ASA daily for 14 days. Video capsule images were assessed by 2 independent expert endoscopists, fully blinded to the treatment group, by using an endoscopic scale.


      Post-ASA VCE detected 10 cases (50%) with mucosal damage not apparent in baseline studies (6 cases had petechiae, 3 had erosions, and 1 had bleeding stigmata in 2 ulcers). The median baseline lac/man ratio (0.021; range, 0.011–0.045) increased after ASA use (0.036; range, 0.007–0.258; P = .08), and the post-ASA lac/man ratio was above the upper end of normal (>0.025) in 10 of 20 volunteers (vs baseline, P < .02). The median baseline fecal calprotectin concentration (6.05 μg/g; range, 1.9–79.2) also increased significantly after ASA use (23.9 μg/g; range, 3.1–75.3; P < .0005), with 3 patients having values above the cutoff (>50 μg/g). Five of 10 subjects with abnormal findings at VCE also had lac/man ratios above the cutoff. Median baseline sucrose urinary excretion (70.0 mg; range, 11.8–151.3) increased significantly after ASA administration (107.0 mg; range, 22.9–411.3; P < .05).


      The short-term administration of low-dose ASA is associated with mucosal abnormalities of the small bowel mucosa, which might have implications in clinical practice.

      Abbreviations used in this paper:

      ASA (acetylsalicylic acid), lac/man ratio (lactulose/mannitol ratio), VCE (video capsule endoscopy)
      To read this article in full you will need to make a payment
      AGA Member Login
      Login with your AGA username and password.
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Purchase one-time access:

      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Antithrombotic Trialists' Collaboration
        Collaborative meta-analysis of randomized trials of antiplatelet therapy for the prevention of death, myocardial infarction, and stroke in high risk patients.
        BMJ. 2002; 324: 71-86
        • Derry S.
        • Loke Y.K.
        Risk of gastrointestinal haemorrhage with long term use of aspirin: meta-analysis.
        BMJ. 2000; 321: 1183-1187
        • Sorensen H.T.
        • Mellemkjaer L.
        • Blot W.J.
        • et al.
        Risk of upper gastrointestinal bleeding associated with use of low dose aspirin.
        Am J Gastroenterol. 2000; 95: 2218-2224
        • Lanas A.
        • Scheiman J.
        Low-dose aspirin and upper gastrointestinal damage: epidemiology, prevention and treatment.
        Curr Med Res Opin. 2007; 23: 163-173
        • Bjarnason I.
        • Hayllar J.
        • Macpherson A.J.
        • et al.
        Side effects of nonsteroidal anti-inflammatory drugs on the small and large intestine in humans.
        Gastroenterology. 1993; 104: 1832-1847
        • Tibble J.A.
        • Sigthorsson G.
        • Foster R.
        • et al.
        High prevalence of NSAID enteropathy as shown by a simple faecal test.
        Gut. 1999; 45: 362-366
        • Bjarnason I.
        • Zanelli G.
        • Prouse P.
        • et al.
        Blood and protein loss via small intestinal inflammation induced by nonsteroidal antiinflammatory drugs.
        Lancet. 1987; 2: 711-714
        • Bjarnason I.
        • Williams P.
        • Smethurst P.
        • et al.
        The effect of NSAIDs and prostaglandins on the permeability of the human small intestine.
        Gut. 1986; 27: 1292-1297
        • Bjarnason I.
        • Peters T.J.
        Intestinal permeability, non-steroidal anti-inflammatory drug enteropathy and inflammatory bowel disease: an overview.
        Gut. 1989; 30: 22-28
        • Davies N.M.
        Non-steroidal anti-inflammatory drug-induced gastrointestinal permeability.
        Aliment Pharmacol Ther. 1998; 12: 303-320
        • Smecuol E.
        • Bai J.C.
        • Sugai E.
        • et al.
        Acute gastrointestinal permeability responses to different non-steroidal anti-inflammatory drugs.
        Gut. 2001; 49: 650-655
        • Iddan G.
        • Meron G.
        • Glukhovsky A.
        • et al.
        Wireless capsule endoscopy.
        Nature. 2000; 405: 417
        • Sigthorsson G.
        • Tibble J.
        • Hayllar J.
        • et al.
        Intestinal permeability and inflammation in patients on NSAIDs.
        Gut. 1998; 43: 506-511
        • Montalto M.
        • Curigliano V.
        • Santoro L.
        • et al.
        Prophylactic aspirin therapy does not increase faecal calprotectin concentrations.
        Eur J Gastroenterol Hepatol. 2006; 18: 965-967
        • Graham D.
        • Opekin A.
        • Willingham F.
        • et al.
        Visible small-intestinal mucosal injury in chronic NSAID users.
        Clin Gastroenterol Hepatol. 2005; 3: 55-59
        • Leung W.K.
        • Bjarnason I.
        • Wong V.W.
        • et al.
        Small bowel enteropathy associated with chronic low-dose aspirin therapy.
        Lancet. 2007; 369: 614
        • Lou H.Y.
        • Chang C.C.
        • Sheu M.T.
        • et al.
        Optimal dose regimens of esomeprazole for gastric acid suppression with minimal influence of the CYP2C19 polymorphism.
        Eur J Clin Pharmacol. 2009; 65: 55-64
        • Shimatani T.
        • Inoue M.
        • Kuroiwa T.
        • et al.
        Rabeprazole 10 mg twice daily is superior to 20 mg once daily for night-time gastric acid suppression.
        Aliment Pharmacol Ther. 2004; 19: 113-122
        • Goldstein J.L.
        • Eisen G.M.
        • Lewis B.
        • et al.
        Video capsule endoscopy to prospectively assess small bowel injury with celecoxib, naproxen plus omeprazole, and placebo.
        Clin Gastroenterol Hepatol. 2005; 3: 133-141
        • Ton H.
        • Brandsnes O.
        • Dale S.
        Improved assay for fecal calprotectin.
        Clin Chim Acta. 2000; 191: 41-54
        • Maiden L.
        • Thjodleifsson B.
        • Theodors A.
        • et al.
        A quantitative analysis of NSAID-induced small bowel pathology by capsule enteroscopy.
        Clin Gastroenterol Hepatol. 2005; 128: 117-118
        • Meddings J.B.
        • Sutherland L.R.
        • Byles N.I.
        • et al.
        Sucrose: a novel permeability marker for gastroduodenal disease.
        Gastroenterology. 1993; 104: 1619-1626
        • Brune K.
        • Schwietzer A.
        • Eckert H.
        Parietal cells of the stomach trap salicylates during absorption.
        Biochem Pharmacol. 1977; 26: 1735-1740
        • Davies N.
        Sustained release and enteric coated NSAIDs: are they really GI safe?.
        J Pharm Pharm Sci. 1999; 2: 5-14
        • Marshall T.A.
        Intestinal perforation following enteral administration of indomethacin.
        J Pediatr. 1985; 106: 277-281