Aspirin, even at a lower dose, can cause stomach ulcers and bleeding, often due to an infection with Helicobacter pylori bacteria.1A L, J S. Low-dose aspirin and upper gastrointestinal damage: epidemiology, prevention and treatment. Current medical research and opinion. 2007;23(1). doi:10.1185/030079907X162656 For those with unexplained sensitivity to aspirin, screening infection can rule out the possibility.
When talking about aspirin, it’s important to talk about mucin. The levels of mucin, a protein found predominantly in mucus, generally acts as a barrier in the intestine. In rats, low levels of mucin reverses fatty liver disease and obesity by reducing inflammation and activating the immune system, mediating through the protein interleukin-22 (IL-22).2Hartmann P, Seebauer CT, Mazagova M, et al. Deficiency of intestinal mucin-2 protects mice from diet-induced fatty liver disease and obesity. Am J Physiol Gastrointest Liver Physiol. 2016;310(5):G310-322. doi:10.1152/ajpgi.00094.2015 IL-22 can functionally substitute for mucin and preserve the integrity of the colon under stress.3Wang X, Ota N, Manzanillo P, et al. Interleukin-22 alleviates metabolic disorders and restores mucosal immunity in diabetes. Nature. 2014;514(7521):237-241. doi:10.1038/nature13564 In the study by Hartmann, a mucin deficiency protected the rats against the diabetes normally induced by a high-fat diet, but some of the markers, such as increased beta-oxidation, or in other words, “fat-burning” metabolism, are concerning.
An interesting Russian study suggests that cells lacking in sufficient metabolic energy could be causal in irritable bowel syndrome and leaky gut syndrome, and they established a causal link between mucin deficiency and gut damage.4Borisova MA, Achasova KM, Morozova KN, et al. Mucin-2 knockout is a model of intercellular junction defects, mitochondrial damage and ATP depletion in the intestinal epithelium. Sci Rep. 2020;10(1):21135. doi:10.1038/s41598-020-78141-4
Interestingly, mice deficient in mucin have protection against alcohol in that their microbiomes do not get shuffled in the same way as ordinary rats, and also they have greater sterility in their guts when devoid of mucin.5Hartmann P, Chen P, Wang HJ, et al. Deficiency of intestinal mucin-2 ameliorates experimental alcoholic liver disease in mice. Hepatology. 2013;58(1):108-119. doi:10.1002/hep.26321 The sterilizing effect of mucin deficiency in the gut would explain why we see reduced levels of endotoxin and thus inflammation.6Hartmann P, Chen P, Wang HJ, et al. Deficiency of intestinal mucin-2 ameliorates experimental alcoholic liver disease in mice. Hepatology. 2013;58(1):108-119. doi:10.1002/hep.26321
a greater antibiotic effect from the alcohol In theory, aspirin would have the same protective effects. Dr. Raymond Peat, PhD speaks about aspirin acclimatization, which takes several days.
Muc2 deficiency significantly reduces lipopolysaccharide in plasma, also known as endotoxin, and protects against alcohol-induced fatty liver disease (AFLD), non-alcoholic fatty liver disease (NAFLD), and obesity with improved glucose homeostasis, reduced inflammation, and upregulation of genes involved in lipolysis and beta-oxidation. Aspirin administration initially increases mucin, including Muc2, but by day 4, an oral dosage of 600 mg inhibits mucin output, which drops below baseline by day 10. Aspirin also lowers nuclear factor-kappaB activity (NFkappa-B) and lowers Muc2; NFkappa-B suppresses cellular apoptosis, promotes cancer, and signals Muc2 induction via deoxycholic acid.
This study aimed to evaluate whether the type of aspirin affects the incidence of gastrointestinal bleeding, particularly in the small intestine. The study involved a retrospective cohort of patients who were taking long-term low-dose aspirin for cardiovascular diseases. The results showed that the type of aspirin did not affect the incidence of overt gastrointestinal bleeding, but enteric-coated aspirin may be associated with an increased incidence of decreased hemoglobin.7Hirata Y, Kataoka H, Shimura T, et al. Incidence of gastrointestinal bleeding in patients with cardiovascular disease: buffered aspirin versus enteric-coated aspirin. Scand J Gastroenterol. 2011;46(7-8):803-809. doi:10.3109/00365521.2011.568522
As little as a 1/3 of a teaspoon of baking soda for every 600 mg of aspirin mitigates the damage done to the stomach.8Bowen BK, Krause WJ, Ivey KJ. Effect of sodium bicarbonate on aspirin-induced damage and potential difference changes in human gastric mucosa. Br Med J. 1977;2(6094):1052-1055. doi:10.1136/bmj.2.6094.1052 Adding baking soda, as in buffered preparations, to aspirin increases its solubility in water, which can reduce the likelihood of any direct damage when contacting the stomach.9Mirrakhimov AE, Ayach T, Barbaryan A, Talari G, Chadha R, Gray A. The Role of Sodium Bicarbonate in the Management of Some Toxic Ingestions. Int J Nephrol. 2017;2017:7831358. doi:10.1155/2017/7831358 Some studies show an advantage of enteric-coated aspirin over buffered aspirin101. Banoob DW, McCloskey WW, Webster W. Risk of gastric injury with enteric- versus nonenteric-coated aspirin. Ann Pharmacother. 2002;36(1):163-166. doi:10.1345/aph.18325 , whereas others show the opposite.11Kelly JP, Kaufman DW, Jurgelon JM, Sheehan J, Koff RS, Shapiro S. Risk of aspirin-associated major upper-gastrointestinal bleeding with enteric-coated or buffered product. Lancet. 1996;348(9039):1413-1416. doi:10.1016/S0140-6736(96)01254-8 The enteric-coated aspirin will not absorb rapidly unless chewed,121. Torborg L. Mayo Clinic Q and A: Coated aspirin may not be as effective at reducing blood clot risk. Mayo Clinic News Network. Published December 4, 2018. Accessed March 15, 2023. https://newsnetwork.mayoclinic.org/discussion/mayo-clinic-q-and-a-coated-aspirin-may-not-be-as-effective-at-reducing-blood-clot-risk/ diminishing its usefulness in a situation with a patient suspected of having a heart attack. Buffered aspirin generally absorbs the fastest of all three forms, whereas enteric-coated aspirin absorbs the slowest 13Latini R, Cerletti C, de Gaetano G, et al. Comparative bioavailability of aspirin from buffered, enteric-coated and plain preparations. Int J Clin Pharmacol Ther Toxicol. 1986;24(6):313-318. 2. Sagar KA, Smyth MR. A comparative bioavailability study of different aspirin formulations using on-line multidimensional chromatography. J Pharm Biomed Anal. 1999;21(2):383-392. doi:10.1016/s0731-7085(99)00177-6. Taking aspirin with food delays its absorption.14Mojaverian P, Rocci ML, Conner DP, Abrams WB, Vlasses PH. Effect of food on the absorption of enteric-coated aspirin: correlation with gastric residence time. Clin Pharmacol Ther. 1987;41(1):11-17. doi:10.1038/clpt.1987.3. Other studies demonstrate that with enteric-coated aspirin, taking it before eating or before sleep reduces digestive upset.15Guo W, Lu W, Xu Y, Wang L, Wei Q, Zhao Q. Relationship between Adverse Gastric Reactions and the Timing of Enteric-Coated Aspirin Administration. Clin Drug Investig. 2017;37(2):187-193. doi:10.1007/s40261-016-0474-z
Food generally delays the absorption of NSAIDs including aspirin, which delays its benefit in pain mitigation.16Moore RA, Derry S, Wiffen PJ, Straube S. Effects of food on pharmacokinetics of immediate release oral formulations of aspirin, dipyrone, paracetamol and NSAIDs – a systematic review. Br J Clin Pharmacol. 2015;80(3):381-388. doi:10.1111/bcp.12628 Aspirin does have an increased number of acute adverse effects compared to other NSAIDs,17Moore RA, Derry S, McQuay HJ, Wiffen PJ. Single dose oral analgesics for acute postoperative pain in adults. Cochrane Database Syst Rev. 2011;(9):CD008659. doi:10.1002/14651858.CD008659.pub2 , but aspirin also has a far safer long-term side effect profile than other NSAIDs, the latter of which have been associated with heart attacks.18Sondergaard KB, Weeke P, Wissenberg M, et al. Non-steroidal anti-inflammatory drug use is associated with increased risk of out-of-hospital cardiac arrest: a nationwide case–time–control study. European Heart Journal – Cardiovascular Pharmacotherapy. 2017;3(2):100-107. doi:10.1093/ehjcvp/pvw041 Another notable effect of aspirin includes its hypoglycemic effect, which can reverse prediabetes and lower cholesterol levels.19Baron SH. Salicylates as Hypoglycemic Agents. Diabetes Care. 1982;5(1):64-71. doi:10.2337/diacare.5.1.64,201. Kim JK, Kim YJ, Fillmore JJ, et al. Prevention of fat-induced insulin resistance by salicylate. J Clin Invest. 2001;108(3):437-446. doi:10.1172/JCI11559
Certain supplements can enhance aspirin absorption, such as caffeine, 21Yoovathaworn KC, Sriwatanakul K, Thithapandha A. Influence of caffeine on aspirin pharmacokinetics. Eur J Drug Metab Pharmacokinet. 1986;11(1):71-76. doi:10.1007/BF03189777 as well as amino acids, such as taurine,22Kimura T, Kim KS, Sezaki H. Effect of taurine on drug absorption from the rat gastrointestinal tract. J Pharmacobiodyn. 1981;4(1):35-41. doi:10.1248/bpb1978.4.35, glycine, tyrosine, glutamic acid, tartaric acid oraspartic acid 23Murtaza G, Karim S, Najam-ul-Haq M, et al. Interaction analysis of aspirin with selective amino acids. Acta Pol Pharm. 2014;71(1):139-143.
Beverages can affect aspirin’s absorption. Milk or orange juice tends to impair absorption, whereas 80-proof spirits or beer can increase bioavailability and encourage faster absorption.24Odou P, Barthélémy C, Robert H. Influence of seven beverages on salicylate disposition in humans. J Clin Pharm Ther. 2001;26(3):187-193. doi:10.1046/j.1365-2710.2001.00344.x The benefits of alcohol on aspirin absorption may be a moot point, however, due to the association between stomach bleeding amongst alcohol users who take NSAIDs such as aspirin.25Kaufman DW, Kelly JP, Wiholm BE, et al. The risk of acute major upper gastrointestinal bleeding among users of aspirin and ibuprofen at various levels of alcohol consumption. Am J Gastroenterol. 1999;94(11):3189-3196. doi:10.1111/j.1572-0241.1999.01517.x
Interestingly, even in spite of other studies showing the increased absorption of aspirin from caffeine administration, coffee had no significant effect on aspirin absorption.26Ibid.
Aspirin can damage the gut through means other than direct contact with the aspirin crystals, however 27Lanas A, Scheiman J. Low-dose aspirin and upper gastrointestinal damage:epidemiology, prevention and treatment. Current Medical Research and Opinion. 2007;23(1):163-173. doi:10.1185/030079907X162656 Topical application or neutralizing aspirin in a solution with baking soda all can help minimize the risk of contact between the gut and aspirin crystals, but any sensitizing effects on the stomach takes days to remediate, and the addition of vitamin K2 to aspirin can be a valuable component in preventing damage.