Why Might It Be Safer to Take NSAIDs Like Ibuprofen on an Empty Stomach?

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Most patients with osteoarthritis in the United States are prescribed nonsteroidal anti-inflammatory drugs called NSAIDs, which include over-the-counter ibuprofen, sold as Advil, or naproxen, sold as Aleve, or prescription-only celecoxib, sold as Celebrex). Unfortunately, primary care practitioners often lack sufficient awareness of the cardiovascular, gastrointestinal, and kidney hazards associated with these drugs. They aren’t alone. Most patients are also unaware of the associated risks.

In my new book How Not to Hurt, in the section entitled “Over-the-Counter to Under-the-Ground,” I explore how side effects from NSAIDs may be one reason why those with osteoarthritis tend to live shorter lives. Every year, complications from NSAIDs hospitalize more than 100,000 Americans and kill 16,500. The drugs do work for osteoarthritis pain, but 10 to 30 percent of people who regularly take NSAIDs develop stomach ulcers. Even just taking doses of regular aspirin can increase the leakiness of our gut. What about buffered aspirin? It doesn’t make a difference. Regular aspirin and Bufferin were both found to produce multiple erosions in the inner lining of the stomach and intestine. Stick a scope down people’s throats, and you can see extensive damage and redness inside 90 percent of individuals taking aspirin or Bufferin at their recommended doses. How many hours does it take for damage to occur? None. It can happen within five minutes.

To reduce the risk of gastrointestinal side effects, don’t exceed the recommended dose (which is something  28 percent of those surveyed said they do), and don’t use multiple NSAIDs at the same time (to which up to  35 percent confess). The risk of major gastrointestinal bleeding is more than  doubled when a single daily low-dose aspirin is combined with another NSAID. Stomach acid-blocking “proton pump inhibitor” drugs are often used to help prevent NSAID-induced ulcers, but long-term use of such drugs has adverse effects of its own, including increased risk of osteoporosis, bone fractures, food poisoning, and pneumonia.

There is a consensus in worldwide recommendations to avoid taking NSAIDs on an empty stomach. Surprisingly, this does not appear to be supported by the available evidence. There don’t appear to be any human studies showing any advantage of taking them with food. Instead, current data point in the opposite direction, because taking them with food reduces their efficacy. Taking ibuprofen on an empty stomach leads to more rapid absorption, producing earlier and higher blood concentrations, and, ultimately, better and longer-lasting pain relief. The same has been found for other over-the-counter analgesics, like aspirin and acetaminophen––Tylenol. Taking these with food may make them less effective. And that’s how, ironically, taking these medicines with food can lead to greater risk, since patients might be tempted to take additional doses sooner, or take more the next time.

NSAIDs also increase the odds of a heart attack by up to 50 percent, which translates into one extra heart attack per 100 to 200 users every year. They also appear to  double the risk of sudden kidney injury in those over age 50. Millions of Americans have their kidneys damaged by these drugs every year. Common NSAIDs like ibuprofen are associated with a threefold increase in the risk of having a stroke. Overall, over-the-counter NSAIDS kill more than 25,000 Americans a year. This places NSAIDs within the top 30 causes of death in the United States. The risks are considered so great at older ages that the American Geriatrics Society recommends opioid drugs over NSAIDs for chronic pain in those older than 75.

The cardiovascular, kidney, and gastrointestinal risks are similar for ibuprofen and naproxen. Prescription-only celecoxib has similar cardiovascular risk, but it seems to cause fewer kidney problems than ibuprofen, and has significantly lower gastrointestinal risk than either of the over-the-counter drugs. The bottom line, given the risks associated with this class of drugs, if their use is deemed necessary, the lowest effective dose should be taken for the shortest possible duration.

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