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NSAIDs: A Pain in the Gut

NSAIDs: A Pain in the Gut

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The gut-protective effects of curcumin and probiotics

Millions of people use non-steroidal anti-inflammatory drugs (NSAIDs) to alleviate the pain of arthritis, headaches, and other painful conditions.[1] Well-known NSAIDs include ibuprofen (Advil, Motrin) naproxen (Aleve), and aspirin. Many other NSAIDs (diclofenac, etc.) are available by prescription.

Although NSAIDs may relieve pain, their use is associated with a broad spectrum of adverse reactions in the liver, kidneys, cardiovascular system, and gastrointestinal (GI) tract.[2]

The side effects of NSAIDs on the gut range from simple dyspepsia (discomfort or pain in the upper abdomen) to life-threatening GI bleeds and perforations.[3],[4],[5],[6],[7] In short, NSAIDs can literally be “a pain in the gut.”

In today’s post we’ll explain the impact of NSAIDs on the gut, and look at how curcumin and probiotics may help protect GI health and even reduce the need for NSAIDs in the long run.

Read the warning label before taking NSAIDs

We now know that microscopic intestinal damage occurs in two-thirds of NSAID users, although most people are unaware that it is happening.[8],[9],[10],[11]

Unfortunately, NSAIDs cause nearly 103,000 hospitalizations and 16,500 deaths annually.[12] One of those hospitalized was a friend of mine, who was taking ibuprofen to manage arthritis pain. She recovered from her ordeal, but only after undergoing surgery to repair the intestinal damage.

It’s not surprising that scientists are searching for ways to support GI health in people taking NSAIDs. Growing evidence suggests that curcumin and probiotics may help shield the gut from NSAID-induced damage.

Curcumin has gut-protective effects

Curcumin strengthens the intestinal barrier and enhances the survival of cells lining the GI tract.

The mucosal lining of the GI tract possesses numerous internal mechanisms to maintain homeostasis. NSAIDs disrupt many of these pathways, however, throwing the whole system into disarray.[13]

First, NSAIDs provoke oxidative stress and impair mitochondrial energy production in the stomach and intestines.[14],[15],[16],[17],[18] The longer NSAIDs are consumed, the worse the oxidative stress.[19] NSAIDs also damage the endoplasmic reticulum (ER), another essential organelle (part of a cell).[20]

Nutraceuticals that reduce oxidative stress and inflammation may help counteract the damaging effects of NSAIDs. Curcuminoids, including curcumin, are bioactive ingredients derived from the Indian spice turmeric. Among its many benefits, curcumin may help protect against NSAID-induced damage.[21],[22],[23]

Curcumin strengthens the intestinal barrier and enhances the survival of cells lining the GI tract.[24],[25] In animal models, the co-administration of curcumin significantly reduced the harmful effects of NSAIDs on the stomach and small intestine, as assessed by a battery of biochemical and histology tests.[26],[27]

Curcumin may reduce the need for NSAIDs

Four reviews concluded that curcumin could reduce pain and improve physical functioning in patients with osteoarthritis.

Osteoarthritis is one of the leading causes of chronic pain in the US, and 65% of all arthritis patients are prescribed NSAIDs for pain management.[28]

Numerous studies suggest that curcumin may alleviate arthritis pain, which is why curcumin is often included in joint support supplements.[29] Taking curcumin may thus reduce the need for NSAIDs and spare the GI tract from unnecessary damage.

The benefits of curcumin were demonstrated in a randomized controlled trial (RCT) of 139 patients with arthritis who received either diclofenac or curcumin (500 mg curcuminoids three times daily) for 28 days. In this study, curcumin was as effective as the NSAID for relief of joint pain.[30]

In a follow up RCT, curcumin was evaluated as an adjunct to NSAIDs in arthritis patients. The group that took curcumin along with diclofenac had greater improvements in pain and quality of life than those receiving diclofenac alone.[31]

In four different systematic reviews published in 2021, all four reviews concluded that curcumin could reduce pain and improve physical functioning in patients with osteoarthritis.[29],[32],[33],[34]

If you are taking curcumin, be sure to select a formulation that is bioavailable. A formulation of curcumin with a combination of hydrophilic carrier, cellulosic derivatives, and natural antioxidants was shown to increase the relative absorption of total curcuminoids 46-times over standard curcumin.[35]

Probiotics support a healthier microbiome

Probiotics may protect the gut from NSAID-induced damage by increasing the populations of friendly bacteria.

NSAIDs also damage the gut by triggering the growth of Gram-negative bacteria (including intestinal pathogens) at the expense of beneficial bacteria.[36],[37],[38] Excessive numbers of Gram-negative bacteria are associated with leaky gut, inflammation, and erosion of the gastrointestinal lining.[39],[40],[41]

Probiotics may help protect the gut from NSAID-induced damage by increasing the populations of friendly bacteria, namely, Lactobacillus and Bifidobacterium.  These probiotic microbes help eliminate pathogens and restore the intestinal barrier. In animals consuming NSAIDs, oral probiotics had a multitude of effects: they decreased oxidative stress and inflammation, minimized the loss of Goblet cells (the cells responsible for creating a protective mucus layer), and reduced the incidence of bleeding and anemia.[39],[42],[43]

In human subjects taking NSAIDs (low-dose aspirin), probiotic supplementation with Lactobacillus casei or Bifidobacterium breve reduced small intestinal injury as assessed with video capsule endoscopy.[44],[45] Probiotic benefits in NSAID users were seen after two to three months of daily supplementation.[44],[45],[46]

Probiotics support healthy joints

As mentioned, NSAIDs disrupt the microbiota by promoting the growth of Gram-negative bacteria. This bacterial group includes pathogens that release bacterial toxins, which in turn activate cartilage and synovium inflammatory pathways.[47],[48],[49],[50] Therefore, probiotics that reduce gut dysbiosis would be expected to reduce joint inflammation as well.

In animal models of arthritis, joint inflammation and pain were alleviated by supplementation with Lactobacillus casei, Lactobacillus rhamnosus, Lactobacillus acidophilus, or a combination of Lactobacillus acidophilus with curcumin and B vitamins.[51],[52],[53],[54]

This proof-of-concept is being translated into the clinic, with initial studies suggesting that probiotic supplementation may even help slow the progression of osteoarthritis.[55],[56]

In one randomized controlled trial, 537 patients with osteoarthritis received probiotic Lactobacillus casei Shirota or a placebo daily for six months.[55] Probiotic supplementation reduced systemic inflammation, as evidenced by a reduction in C-reactive protein (CRP), a protein that increases when there’s inflammation in the body. Importantly, measures of joint pain, stiffness, and physical functioning, were significantly improved in the probiotic group compared with placebo.  Further studies are warranted to confirm these findings.


If you are taking NSAIDs, consider supplementing with curcumin and probiotics to protect your gut. As an added bonus, these natural products may reduce the need for NSAIDs over the long term.

You may also enjoy the following articles:

Understanding Inflammation
Can Probiotics Soothe IBS?
Bouncing Back After Antibiotic Use: Probiotics to the Rescue!

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The information provided is for educational purposes only. Consult your physician or healthcare provider if you have specific questions before instituting any changes in your daily lifestyle including changes in diet, exercise, and supplement use.

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