Share this post
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. 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.
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.,,,, 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.,,,
Unfortunately, NSAIDs cause nearly 103,000 hospitalizations and 16,500 deaths annually. 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.
First, NSAIDs provoke oxidative stress and impair mitochondrial energy production in the stomach and intestines.,,,, The longer NSAIDs are consumed, the worse the oxidative stress. NSAIDs also damage the endoplasmic reticulum (ER), another essential organelle (part of a cell).
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.,,
Curcumin strengthens the intestinal barrier and enhances the survival of cells lining the GI tract., 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.,
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.
Numerous studies suggest that curcumin may alleviate arthritis pain, which is why curcumin is often included in joint support supplements. 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.
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.
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.,,,
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.
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.,, Excessive numbers of Gram-negative bacteria are associated with leaky gut, inflammation, and erosion of the gastrointestinal lining.,,
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.,,
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., Probiotic benefits in NSAID users were seen after two to three months of daily supplementation.,,
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.,,, 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.,,,
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.,
In one randomized controlled trial, 537 patients with osteoarthritis received probiotic Lactobacillus casei Shirota or a placebo daily for six months. 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:
Can Probiotics Soothe IBS?
Bouncing Back After Antibiotic Use: Probiotics to the Rescue!
 Zhou Y, et al. Trends in the use of aspirin and nonsteroidal anti-inflammatory drugs in the general U.S. population. Pharmacoepidemiol Drug Saf. 2014 Jan;23(1):43-50.
 Scarpignato C, Hunt RH. Nonsteroidal antiinflammatory drug-related injury to the gastrointestinal tract: clinical picture, pathogenesis, and prevention. Gastroenterol Clin North Am. 2010 Sep;39(3):433-64.
 Goldstein JL, Cryer B. Gastrointestinal injury associated with NSAID use: a case study and review of risk factors and preventative strategies. Drug Healthc Patient Saf. 2015 Jan 22;7:31-41.
 Sostres C, et al. Nonsteroidal anti-inflammatory drugs and upper and lower gastrointestinal mucosal damage. Arthritis Res Ther. 2013;15 Suppl 3(Suppl 3):S3.
 Bindu S, et al. Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: a current perspective. Biochem Pharmacol. 2020 Oct;180:114147.
 Yap PRY, Goh KL. Non-steroidal anti-inflammatory drugs (NSAIDs) induced dyspepsia. Curr Pharm Des. 2015;21(35):5073-81.
 Tai FWD, McAlindon ME. NSAIDs and the small bowel. Curr Opin Gastroenterol. 2018 May;34(3):175-82.
 Maiden L. Capsule endoscopic diagnosis of nonsteroidal antiinflammatory drug-induced enteropathy. J Gastroenterol. 2009;44 Suppl 19:64-71.
 Sidhu R, et al. Undisclosed use of nonsteroidal anti-inflammatory drugs may underlie small-bowel injury observed by capsule endoscopy. Clin Gastroenterol Hepatol. 2010 Nov;8(11):992-5.
 Graham DY, et al. Visible small-intestinal mucosal injury in chronic NSAID users. Clin Gastroenterol Hepatol. 2005;3:55–9.
 Adebayo D, Bjarnason I. Is non-steroidal anti-inflammatory drug (NSAID) enteropathy clinically more important than NSAID gastropathy? Postgrad Med J. 2006 Mar;82(965):186-91.
 American Gastroenterological Association. Study shows long-term use of NSAIDs causes severe intestinal damage [Internet]. Bethesda (MD): Science Daily: 2005 [cited 2022 Jan 15]. Available from: https://www.sciencedaily.com/releases/2005/01/050111123706.htm
 Scarpignato C. Nonsteroidal anti-inflammatory drugs: how do they damage gastroduodenal mucosa? Dig Dis. 1995 Jan;13 Suppl 1:9-39.
 Nagano Y, et al. NSAIDs and acidic environment induce gastric mucosal cellular mitochondrial dysfunction. Digestion. 2012;85(2):131-5.
 Matsui H, et al. The pathophysiology of non-steroidal anti-inflammatory drug (NSAID)-induced mucosal injuries in stomach and small intestine. J Clin Biochem Nutr. 2011 Mar;48(2):107-11.
 Trujillo J, et al. Mitochondria as a target in the therapeutic properties of curcumin. Arch Pharm (Weinheim). 2014 Dec;347(12):873-84.
 Bhatt AP, et al. Nonsteroidal anti-inflammatory drug-induced leaky gut modeled using polarized monolayers of primary human intestinal epithelial cells. ACS Infect Dis. 2018 Jan 12;4(1):46-52.
 Somasundaram S, et al. Uncoupling of intestinal mitochondrial oxidative phosphorylation and inhibition of cyclooxygenase are required for the development of NSAID-enteropathy in the rat. Aliment Pharmacol Ther. 2000 May;14(5):639-50.
 Nawaz H, et al. Chronological effects of non-steroidal anti-inflammatory drug therapy on oxidative stress and antioxidant status in patients with rheumatoid arthritis. Clin Rheumatol. 2021 May;40(5):1767-78.
 Tsutsumi S, et al. Endoplasmic reticulum stress response is involved in nonsteroidal anti-inflammatory drug-induced apoptosis. Cell Death Differ. 2004 Sep;11(9):1009-16.
 Kwiecien S, et al. Curcumin: a potent protectant against esophageal and gastric disorders. Int J Mol Sci. 2019 Mar 24;20(6):1477.
 Morsy MA, El-Moselhy MA. Mechanisms of the protective effects of curcumin against indomethacin-induced gastric ulcer in rats. Pharmacology. 2013;91(5-6):267-74.
 Wang J, et al. Curcumin improves intestinal barrier function: modulation of intracellular signaling, and organization of tight junctions. Am J Physiol Cell Physiol. 2017 Apr 1;312(4):C438-45.
 Loganes C, et al. Curcumin anti-apoptotic action in a model of intestinal epithelial inflammatory damage. Nutrients. 2017 Jun 6;9(6):578.
 Cho JA, Curcumin utilizes the anti-inflammatory response pathway to protect the intestine against bacterial invasion. Nutr Res Pract. 2015 Apr;9(2):117-22.
 Singh DP, et al. Curcumin, a component of turmeric, efficiently prevents diclofenac sodium-induced gastroenteropathic damage in rats: a step towards translational medicine. Food Chem Toxicol. 2017 Oct;108(Pt A):43-52.
 Sivalingam N, et al. Curcumin attenuates indomethacin-induced oxidative stress and mitochondrial dysfunction. Arch Toxicol. 2008 Jul;82(7):471-81.
 Heffernan SN, Conway GE. Nutraceutical alternatives to pharmaceutical analgesics in osteoarthritis. Pain Management: Practices, Novel Therapies and Bioactives. 2021 Mar 1;12:161.
 Hsiao AF, et al. The efficacy of high- and low-dose curcumin in knee osteoarthritis: a systematic review and meta-analysis. Complement Ther Med. 2021 Dec;63:102775.
 Shep D, et al. Safety and efficacy of curcumin versus diclofenac in knee osteoarthritis: a randomized open-label parallel-arm study. Trials. 2019 Apr 11;20(1):214.
 Shep D, et al. Efficacy and safety of combination of curcuminoid complex and diclofenac versus diclofenac in knee osteoarthritis: a randomized trial. Medicine (Baltimore). 2020 Apr;99(16):e19723.
 Paultre K, et al. Therapeutic effects of turmeric or curcumin extract on pain and function for individuals with knee osteoarthritis: a systematic review. BMJ Open Sport Exerc Med. 2021 Jan 13;7(1):e000935.
 Wang Z, et al. Efficacy and safety of turmeric extracts for the treatment of knee osteoarthritis: a systematic review and meta-analysis of randomised controlled trials. Curr Rheumatol Rep. 2021 Jan 28;23(2):11.
 Zeng L, et al. The efficacy and safety of Curcuma longa extract and curcumin supplements on osteoarthritis: a systematic review and meta-analysis. Biosci Rep. 2021 Jun 25;41(6):BSR20210817.
 Jäger R, et al. Comparative absorption of curcumin formulations. Nutrition J. 2014 Dec;13(1):1-8.
 Wang X, et al. Gut microbiota in NSAID enteropathy: new insights from inside. Front Cell Infect Microbiol. 2021 Jul 6;11:679396.
 Mayo SA, et al. Indomethacin injury to the rat small intestine is dependent upon biliary secretion and is associated with overgrowth of enterococci. Physiol Rep. 2016 Mar;4(6):e12725.
 Kinouchi T, et al. Culture supernatants of Lactobacillus acidophilus and Bifidobacterium adolescentis repress ileal ulcer formation in rats treated with a nonsteroidal antiinflammatory drug by suppressing unbalanced growth of aerobic bacteria and lipid peroxidation. Microbiol Immunol. 1998;42(5):347-55.
 Wallace JL, et al. Proton pump inhibitors exacerbate NSAID-induced small intestinal injury by inducing dysbiosis. Gastroenterology. 2011 Oct;141(4):1314-22,
 Dalby AB, et al. Culture-independent analysis of indomethacin-induced alterations in the rat gastrointestinal microbiota. Appl Environ Microbiol. 2006 Oct;72(10):6707-15.
 Takeuchi K, Satoh H. NSAID-induced small intestinal damage–roles of various pathogenic factors. Digestion. 2015;91(3):218-32.
 Monteros MJM, et al. Probiotic lactobacilli as a promising strategy to ameliorate disorders associated with intestinal inflammation induced by a non-steroidal anti-inflammatory drug. Sci Rep. 2019 Nov 14;9(1):16796.
 Yoshihara T, et al. The protective effect of Bifidobacterium bifidum G9-1 against mucus degradation by Akkermansia muciniphila following small intestine injury caused by a proton pump inhibitor and aspirin. Gut Microbes. 2020 Sep 2;11(5):1385-1404.
 Endo H, et al. Efficacy of Lactobacillus casei treatment on small bowel injury in chronic low-dose aspirin users: a pilot randomized controlled study. J Gastroenterol 2011;46:894-905.
 Mortensen B, et al. Bifidobacterium breve Bif195 protects against small-intestinal damage caused by acetylsalicylic acid in healthy volunteers. Gastroenterology. 2019 Sep;157(3):637-46.
 Montalto M, et al. Clinical trial: the effects of a probiotic mixture on non-steroidal anti-inflammatory drug enteropathy – a randomized, double-blind, cross-over, placebo-controlled study. Aliment Pharmacol Ther. 2010;32:209-14.
 Guido G, et al. Gut permeability and osteoarthritis, towards a mechanistic understanding of the pathogenesis: a systematic review. Ann Med. 2021 Dec;53(1):2380-90.
 Chisari E, et al. The relation between the gut microbiome and osteoarthritis: a systematic review of literature. PLoS One. 2021 Dec 16;16(12):e0261353.
 Chen WLK, et al. Synergistic action of diclofenac with endotoxin-mediated inflammation exacerbates intestinal injury in vitro. ACS Infect Dis. 2021 Apr 9;7(4):838-48.
 Huang ZY, et al. Both systemic and local lipopolysaccharide (LPS) burden are associated with knee OA severity and inflammation. Osteoarthritis Cartilage. 2016 Oct;24(10):1769-75.
 So JS, et al. Lactobacillus casei enhances type II collagen/glucosamine-mediated suppression of inflammatory responses in experimental osteoarthritis. Life Sci. 2011 Feb 14;88(7-8):358-66.
 Lee SH, et al. Lactobacillus acidophilus ameliorates pain and cartilage degradation in experimental osteoarthritis. Immunol Lett. 2018 Nov;203:6-14.
 Jhun J, et al. Oral administration of Lactobacillus rhamnosus ameliorates the progression of osteoarthritis by inhibiting joint pain and inflammation. Cells. 2021 Apr 29;10(5):1057.
 Jhun J, et al. Combination treatment with Lactobacillus acidophilus LA-1, vitamin B, and curcumin ameliorates the progression of osteoarthritis by inhibiting the pro-inflammatory mediators. Immunol Lett. 2020 Dec;228:112-21.
 Lei M, et al. The effect of probiotic Lactobacillus casei Shirota on knee osteoarthritis: a randomised double-blind, placebo-controlled clinical trial. Benef Microbes. 2017 Oct 13;8(5):697-703.
 Lyu JL, et al. Oral intake of Streptococcus thermophilus improves knee osteoarthritis degeneration: a randomized, double-blind, placebo-controlled clinical study. Heliyon. 2020 Apr 25;6(4):e03757.
Share this post
Marina MacDonald, MS, PhD
Fighting Fatty Liver, Part 1 of 2
How the gut, microbes, inflammation, and diet affect the liver, and what to do about it The fatty liver epidemic Sedentary lifestyles, nutrient-poor diets, chemical exposures, and an excess of sugar and refined foods are wreaking havoc on and in our bodies more than ever before. And the effects aren’t just cosmetic – beyond…
The Healing Power of Colostrum
From infants to top-notch athletes to the critically ill, this “first milk” provides immune and gastrointestinal benefits What’s the nutritional superfood almost all of us have had at some time in our life, and new mothers, dairy farmers, and Ob/Gyns know best? It’s colostrum, the first milk that comes at birth. It actually comes…
What is Bowel Tolerance?
A guide to dosing vitamin C, magnesium, and other nutrients We often talk about taking vitamin C and magnesium to “bowel tolerance” – but what does that mean? Dosing a supplement to bowel tolerance means taking the highest dose of that supplement possible without causing loose, watery stools (diarrhea). If you’re taking vitamin C…
Soothing heartburn naturally In last week’s post we described the real cause of gastroesophageal reflux disease (GERD) and explored why conventional strategies for managing the condition can come with negative health risks over time. Today we’ll take a look at some simple, natural, remedies for alleviating reflux at its root cause, primarily by (1)…
Mastering Irritable Bowel Syndrome – Knowledge is Power
From enzymes to eating habits, there is hope Everyone has episodes of digestive discomfort from time-to-time. Unfortunately, some of us experience digestive problems chronically. It’s then that the doctor is seen, and most often, the diagnosis is irritable bowel syndrome, commonly known as IBS. The physician’s recommendations may include a gentle laxative, fiber, water,…
Candida Overgrowth – Herbal Medicine to the Rescue!
A Naturopathic Doctor’s Approach Most integrative medicine physicians who have been in clinical practice for a number of years will inevitably encounter a multitude of patients who have had their health negatively impacted by some form of Candida spp. infection. Fungal infections are estimated to occur in several million people each year, and recent…
Subscribe for Updates
- Botanicals (57)
- GI Health (53)
- Healthy Aging (122)
- Immune Support (41)
- In The News (42)
- Kids Health (21)
- Stress and Relaxation (50)
- Video (9)
- Vitamins & Minerals (52)
Latest Issue of FOCUS Newsletter Available Now!
About Nutrition In Focus
Subscribe for Updates
Contents of this website are for the purpose of information and education only,
and not a guide to diagnosis or treatment of a particular disorder or its symptoms.
Copyright©2018-2021 Allergy Research Group®. All Rights Reserved.