NSAID painkillers like Advil and Aleve cause more than 100,000 hospitalizations and 16,500 deaths each year in the United States alone. Up to 30% of regular users develop stomach ulcers, yet most patients and doctors remain unaware of the true risks.
Why Might It Be Safer to Take NSAIDs Like Ibuprofen on an Empty Stomach?
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Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.
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.
Please consider volunteering to help out on the site.
- Cooper C, Chapurlat R, Al-Daghri N, et al. Safety of Oral Non-Selective Non-Steroidal Anti-Inflammatory Drugs in Osteoarthritis: What Does the Literature Say? Drugs Aging. 2019;36(S1):15-24.
- Laine L. Nonsteroidal anti-inflammatory drug gastropathy. Gastrointest Endosc Clin N Am. 1996;6(3):489-504.
- Sorensen HT, Mellemkjaer L, Blot WJ, et al. Risk of upper gastrointestinal bleeding associated with use of low-dose aspirin. Am J Gastroenterol. 2000;95(9):2218-2224.
- Dahal K, Sharma SP, Kaur J, Anderson BJ, Singh G. Efficacy and Safety of Proton Pump Inhibitors in the Long-Term Aspirin Users: A Meta-Analysis of Randomized Controlled Trials. Am J Ther. 2017;24(5):e559-e569.
- Moore 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.
- Hilmer SN, MacPherson R. Effects of food on pharmacokinetics of immediate release oral formulations of simple analgesics: potential implications for drug use, safety and efficacy. Br J Clin Pharmacol. 2015;80(6):1243-1244.
- Rainsford KD, Bjarnason I. NSAIDs: take with food or after fasting? J Pharm Pharmacol. 2012;64(4):465-469.
- Bally M, Dendukuri N, Rich B, et al. Risk of acute myocardial infarction with NSAIDs in real world use: bayesian meta-analysis of individual patient data. BMJ. 2017;357:j1909.
- Zhang X, Donnan PT, Bell S, Guthrie B. Non-steroidal anti-inflammatory drug induced acute kidney injury in the community dwelling general population and people with chronic kidney disease: systematic review and meta-analysis. BMC Nephrol. 2017;18(1):256.
- Ho KY, Cardosa MS, Chaiamnuay S, et al. Practice Advisory on the Appropriate Use of NSAIDs in Primary Care. J Pain Res. 2020;13:1925-1939.
- Challa KT, Arja SB, Ponduchi M, Snigdha BM. Lack of Patient Knowledge Regarding the Adverse Effects of Analgesics With High Doses Leading to Elevation of Creatinine and Major Consequences – A Case Report. Cureus. 2020;12(10):e10891.
- Wolfarth B, Speed C, Raymuev K, Vanden Bossche L, Migliore A. Managing pain and inflammation associated with musculoskeletal disease: time for a change? Curr Med Res Opin. 2022;38(10):1695-1701.
- “American Geriatrics Society Recommends Opioids as Second-Line Therapy for Chronic Pain, Instead of NSAIDs,” Topics in Pain Management 25, no. 1 (August 2009): 9–10.
- Nissen SE, Yeomans ND, Solomon DH, et al. Cardiovascular Safety of Celecoxib, Naproxen, or Ibuprofen for Arthritis. N Engl J Med. 2016;375(26):2519-2529.
- Cryer B, Barnett MA, Wagner J, Wilcox CM. Overuse and Misperceptions of Nonsteroidal Anti-inflammatory Drugs in the United States. Am J Med Sci. 2016;352(5):472-480.
- Cryer B, Barnett MA, Wagner J, Wilcox CM. Overuse and Misperceptions of Nonsteroidal Anti-inflammatory Drugs in the United States. Am. J. Med. Sci. 2016;352(5):472-480.
- Ungprasert P, Cheungpasitporn W, Crowson CS, Matteson EL. Individual non-steroidal anti-inflammatory drugs and risk of acute kidney injury: A systematic review and meta-analysis of observational studies. Eur J Intern Med. 2015;26(4):285-291.
- Shah S, Mehta V. Controversies and advances in non-steroidal anti-inflammatory drug (NSAID) analgesia in chronic pain management. Postgrad Med J. 2011;88(1036):73-78.
- Lambert G, Schmidt A, Schwarzkopf K, Lanspa S. Effect of Aspirin Dose on Gastrointestinal Permeability. Int J Sports Med. 2012;33(06):421-425.
- Hoftiezer JW, O’Laughlin JC, Ivey KJ. Effects of 24 hours of aspirin, Bufferin, paracetamol and placebo on normal human gastroduodenal mucosa. Gut. 1982;23(8):692-697.
- Ivey KJ, Baskin WN, Krause WJ, Terry B. Effect of aspirin and acid on human jejunal mucosa. An ultrastructural study. Gastroenterology. 1979;76(1):50-56.
Motion graphics by Avo Media
Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.
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.
Please consider volunteering to help out on the site.
- Cooper C, Chapurlat R, Al-Daghri N, et al. Safety of Oral Non-Selective Non-Steroidal Anti-Inflammatory Drugs in Osteoarthritis: What Does the Literature Say? Drugs Aging. 2019;36(S1):15-24.
- Laine L. Nonsteroidal anti-inflammatory drug gastropathy. Gastrointest Endosc Clin N Am. 1996;6(3):489-504.
- Sorensen HT, Mellemkjaer L, Blot WJ, et al. Risk of upper gastrointestinal bleeding associated with use of low-dose aspirin. Am J Gastroenterol. 2000;95(9):2218-2224.
- Dahal K, Sharma SP, Kaur J, Anderson BJ, Singh G. Efficacy and Safety of Proton Pump Inhibitors in the Long-Term Aspirin Users: A Meta-Analysis of Randomized Controlled Trials. Am J Ther. 2017;24(5):e559-e569.
- Moore 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.
- Hilmer SN, MacPherson R. Effects of food on pharmacokinetics of immediate release oral formulations of simple analgesics: potential implications for drug use, safety and efficacy. Br J Clin Pharmacol. 2015;80(6):1243-1244.
- Rainsford KD, Bjarnason I. NSAIDs: take with food or after fasting? J Pharm Pharmacol. 2012;64(4):465-469.
- Bally M, Dendukuri N, Rich B, et al. Risk of acute myocardial infarction with NSAIDs in real world use: bayesian meta-analysis of individual patient data. BMJ. 2017;357:j1909.
- Zhang X, Donnan PT, Bell S, Guthrie B. Non-steroidal anti-inflammatory drug induced acute kidney injury in the community dwelling general population and people with chronic kidney disease: systematic review and meta-analysis. BMC Nephrol. 2017;18(1):256.
- Ho KY, Cardosa MS, Chaiamnuay S, et al. Practice Advisory on the Appropriate Use of NSAIDs in Primary Care. J Pain Res. 2020;13:1925-1939.
- Challa KT, Arja SB, Ponduchi M, Snigdha BM. Lack of Patient Knowledge Regarding the Adverse Effects of Analgesics With High Doses Leading to Elevation of Creatinine and Major Consequences – A Case Report. Cureus. 2020;12(10):e10891.
- Wolfarth B, Speed C, Raymuev K, Vanden Bossche L, Migliore A. Managing pain and inflammation associated with musculoskeletal disease: time for a change? Curr Med Res Opin. 2022;38(10):1695-1701.
- “American Geriatrics Society Recommends Opioids as Second-Line Therapy for Chronic Pain, Instead of NSAIDs,” Topics in Pain Management 25, no. 1 (August 2009): 9–10.
- Nissen SE, Yeomans ND, Solomon DH, et al. Cardiovascular Safety of Celecoxib, Naproxen, or Ibuprofen for Arthritis. N Engl J Med. 2016;375(26):2519-2529.
- Cryer B, Barnett MA, Wagner J, Wilcox CM. Overuse and Misperceptions of Nonsteroidal Anti-inflammatory Drugs in the United States. Am J Med Sci. 2016;352(5):472-480.
- Cryer B, Barnett MA, Wagner J, Wilcox CM. Overuse and Misperceptions of Nonsteroidal Anti-inflammatory Drugs in the United States. Am. J. Med. Sci. 2016;352(5):472-480.
- Ungprasert P, Cheungpasitporn W, Crowson CS, Matteson EL. Individual non-steroidal anti-inflammatory drugs and risk of acute kidney injury: A systematic review and meta-analysis of observational studies. Eur J Intern Med. 2015;26(4):285-291.
- Shah S, Mehta V. Controversies and advances in non-steroidal anti-inflammatory drug (NSAID) analgesia in chronic pain management. Postgrad Med J. 2011;88(1036):73-78.
- Lambert G, Schmidt A, Schwarzkopf K, Lanspa S. Effect of Aspirin Dose on Gastrointestinal Permeability. Int J Sports Med. 2012;33(06):421-425.
- Hoftiezer JW, O’Laughlin JC, Ivey KJ. Effects of 24 hours of aspirin, Bufferin, paracetamol and placebo on normal human gastroduodenal mucosa. Gut. 1982;23(8):692-697.
- Ivey KJ, Baskin WN, Krause WJ, Terry B. Effect of aspirin and acid on human jejunal mucosa. An ultrastructural study. Gastroenterology. 1979;76(1):50-56.
Motion graphics by Avo Media
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Why Might It Be Safer to Take NSAIDs Like Ibuprofen on an Empty Stomach?
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