Acetylsalicylic acid works by irreversibly disabling the COX enzymes to block the cascade [Figure 1]. NSAIDs have evolved from blocking both COX-1 and COX-2 to selectively only blocking COX-2 in order to inhibit the inflammatory response and reduce the production of inflammatory prostaglandins and thromboxanes. The major push to develop the selective COX-2 inhibitors has been the recognition of significant complications associated with the nonselective COX-1 and COX-2 NSAIDs. Nonselective NSAIDs’ major side effects include significant gastrointestinal upset, gastritis, ulceration, hemorrhage, and even death. By locking COX-1, which also normally acts to protect the gastrointestinal mucosa, nonselective NSAIDs and aspirin can cause significant gastric tissue damage.[34,51,78,91,3,101,115]

Traditional wisdom says that NSAID pain relievers only damage your gut lining if you take them every day for a long time, but recent research disagrees. High-level athletes with stress-related intestinal damage tried taking ibuprofen to improve muscle soreness and recovery. Ibuprofen ended up damaging their gut lining even further after just a couple weeks; it increased inflammation and made their original pain issues worse.[3] In fact, a single dose of aspirin can significantly increase your intestinal permeability.[4]