Wisdom Wednesday: NSAIDs

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used OTC (over-the-counter) drugs in America. They differ in potency and duration of action. They also differ in their tendency to cause ulcers and bleeding based on their relative inhibition of COX-1 and COX-2.

Cyclooxygenase (COX) is an enzyme that is responsible for the formation of prostanoids. The three main groups of prostanoids – prostaglandins, prostacyclins, and thromboxanes – are each involved in the inflammatory response.

However, some of these chemical groups, especially the prostaglandins, produce anti-inflammatory compounds as well. The omega 3 fatty acids (like fish and flax seed oil) are used to make PG-3 (prostaglandin 3) which is anti-inflammatory and the omega 6 fatty acids (like evening primrose and black current seed oil) make the PG-1 series, also anti-inflammatory.

So while reducing inflammatory compounds that produce pain, NSAIDs also reduce the anti-inflammatory compounds that provide relief. These anti-inflammatory compounds also protect and maintain the lining of the GI tract, protect the liver, heart, and other tissues of the body.

Traditional NSAIDs are considered “nonselective” because they inhibit both COX-1 and Cox-2. It is the COX-1 inhibition that is associated with most of the side effects. Bleeding, ulcers, and perforation of the stomach or intestine can occur at any time without warning. Aspirin and Advil (ibuprofen) are the most common “nonselective” NSAIDs.

Celebrex (Aleve) was the first selective COX-2 inhibitor introduced in the late 1990s. Subsequent COX-2 inhibitors Vioxx and Bextra were removed from the market when it was discovered that COX-2 inhibitors are associated with an increased risk of heart attack. Two other COX-2 inhibitors Arcoxia and Prexige have so far been rejected by the FDA. Celebrex remains as the only COX-2 inhibitor available in the United States.



Aspirin is the only NSAID that inhibits the clotting of blood for a prolonged period of time, four to seven days. For many years it was recommended as a preventative for heart attacks. However, about 10 years ago retrospective studies showed the risk of side effects was much greater than any possible benefit from taking baby aspirin daily. Aspirin is still recommended for patients who have had a previous heart attack, but not as primary prevention for the rest of the population. Despite this “standard of care” I still encounter new patients every week that have been advised by their physician to take a baby aspirin daily with no history of heart disease.

Each year over 16,000 people in the U.S. die from taking NSAIDs. Over one third have little or no warning. The most common cause of death is internal bleeding, followed by liver failure and heart attack. It amazes me that the third most common cause of death is so commonly cited as the very reason the patient was taking aspirin – to prevent heart attacks.

This research was first published many years ago in the BMJ (British Medical Journal) and was vehemently denied by Big Pharm. They had done their own studies, with similar results and failed to publish. Somehow, no American medical journal was willing to publish a negative study on NSAIDs.

The Bottom Line:
NSAIDs are powerful drugs that have serious and even fatal side effects. If you must take an NSAID for relief of pain and inflammation, consider whether you are going to use a non-selective NSAID like Advil or a COX-2 inhibitor (Aleve or Celebrex). Each has its’ own risks to weigh against your health history. Limit the use to 3 days, less if possible. Consider other options – The omega 3 and omega 6 fatty acids have similar anti-inflammatory properties without the side effects. Turmeric (Curcumin), ginger, and Boswellia also are excellent anti-inflammatory herbs.