If you’ve ever dealt with arthritis, period pain, post-exercise soreness, or a headache, chances are you’ve popped an NSAID! Non-steroidal anti-inflammatory drugs (NSAIDs) are among the drugs most commonly used by adults in the United States, heavily utilized for their pain-relieving and anti-inflammatory properties.

While NSAIDs can certainly be helpful for alleviating pain and inflammation, they also come with a hefty list of potential side effects that can compromise long-term health. In this article, we’ll dive into how NSAIDs work, the potential problems posed by heavy NSAID use, and 6 effective natural alternatives to NSAIDs.

How Do NSAIDs Work?

Non-steroidal anti-inflammatory drugs (NSAIDs) block the synthesis of prostaglandins, lipid-based signaling molecules involved in inflammation and pain sensation. They do this by inhibiting the activity of cyclooxygenase (COX) enzymes. (Source)

However, prostaglandins and COX enzymes aren’t just involved in inflammation and pain sensation. These crucial signaling molecules also influence the integrity of cells lining the gastrointestinal tract, the liver and kidneys, and connective tissues. Therefore, NSAIDs can affect the body in ways that expand far beyond pain and inflammation relief. The far-reaching effects of NSAIDs explain why these drugs can come with a host of side effects. (Source)

The Side Effects of NSAIDs

COX enzymes have far-reaching effects on the body. Because of this COX inhibitors, such as NSAIDs, can have unintended effects on many aspects of the body besides pain reduction.  

NSAIDs Can Promote Gastric Ulcers and Leaky Gut

COX enzymes help maintain the integrity of the stomach lining and the intestinal barrier, the semipermeable layer of cells that regulates the passage of substances, including nutrients and water, from the intestine into the rest of the body. (Source)

Inhibition of COX enzymes can compromise the stomach and intestinal barriers. In the stomach, this process can lead to gastric ulcer formation, a known side effect of NSAIDs. In the intestines, this process can promote “leaky gut,” in which the intestinal barrier becomes excessively permeable, allowing substances, such as bacterial toxins, to “leak” from the gut into the bloodstream. Leaky gut is implicated in autoimmunity, so excessive NSAID use may be problematic for people with autoimmune diseases. (Source)

In addition, several studies have raised concerns about the potential of NSAIDs to exacerbate inflammatory bowel disease (IBD), though the findings are not definitive. However, natural alternatives to NSAIDs may be preferable for managing pain in IBD. (Source)

NSAIDs May Disrupt the Gut Microbiome

In addition to promoting gastric ulcers and leaky gut, research shows that NSAIDs can affect the composition and function of the gut microbiome. NSAIDs may reduce levels of beneficial gut bacteria, such as Lactobacillus species, and may trigger dysbiosis, which is implicated in the development of autoimmunity. (Source, Source)

NSAIDs May Promote Mitochondrial Dysfunction

Mitochondria are tiny structures inside our cells that make cellular energy, or ATP. Without sufficient ATP, our bodies can’t function properly! Emerging research indicates that NSAIDs can harm these cellular energy “factories,” preventing efficient ATP production (Source)

The long-term health implications of NSAID-induced mitochondrial damage are unclear. However, mitochondrial dysfunction is linked to autoimmunity, making NSAID-induced declines in mitochondrial function potentially relevant for individuals with autoimmune diseases. (Source)

Other Side Effects of NSAIDs

Other potential adverse effects of NSAIDs include kidney damage, liver damage, and decreased bone density. NSAIDs may harm the kidneys by reducing blood flow to these vital organs. They can damage the liver by impairing ATP synthesis within liver cells, thereby preventing liver cells from functioning properly. In bone tissue, NSAIDs may disrupt the balance between bone building and bone breakdown (resorption), contributing to a net loss of bone mass. (Source, Source, Source)

NSAIDs and Autoimmunity: What’s the Connection?

NSAIDs are often recommended to and used by individuals with autoimmune disease to relieve pain and inflammation. For example, up to 80% of patients with systemic lupus erythematosus are treated with NSAIDs for musculoskeletal aches and pains and headaches. NSAIDs are also often one of the very first therapies recommended for people with rheumatoid arthritis. However, as we discussed earlier, NSAIDs also carry a risk of harming the gut, which plays a major role in autoimmune disease. (Source, Source)

Given the potential adverse effects of NSAIDs on the gut, mitochondria, and other organs, natural alternatives to NSAIDs are in demand. Next, let’s review 6 potent natural alternatives to NSAIDs that can alleviate pain and inflammation without untoward side effects.

6 Natural Alternatives to NSAIDs

The natural world is full of plants with anti-inflammatory and pain-relieving properties. White willow bark, tart cherries, ginger, curcumin, and fish oil contain compounds that work on similar biochemical pathways as NSAIDs and alleviate pain and inflammation without the detrimental side effects of NSAID medications.

1. White Willow Bark: A Natural Alternative to NSAIDs

White willow bark comes from the white willow tree, Salix alba. White willow bark has been used by humans for millennia for its anti-inflammatory, fever-reducing, and pain-relieving properties. Modern day clinical research indicates that white willow bark is indeed an effective anti-inflammatory and pain-relieving botanical, making it an excellent natural alternative to NSAIDs. According to the research, white willow bark can attenuate lower back, osteoarthritis, and rheumatic pain. (Source, Source)

Aspirin, or acetylsalicylic acid, is a synthetic drug based on salicin, one of the primary phytochemicals found in willow bark. However, white willow bark also contains other bioactive compounds that may contribute to its anti-inflammatory properties. These include salicylates, which inhibit prostaglandin E2, a potent inflammatory mediator, and procyanidins, which inhibit the production of the inflammatory cytokine NF-κB. (Source, Source)

White willow bark is typically taken either as an alcohol-based tincture or an encapsulated supplement. Importantly, white willow bark should not be consumed by women who are pregnant or nursing or people with a known sensitivity to aspirin.

2. Tart Cherries

Tart cherries are fruits from the Prunus cerasus tree that were first cultivated in France in the 18th century. There are several varieties of tart cherries; Montmorency tart cherries are one of the most common commercially available varieties.

Tart cherries contain an array of anti-inflammatory compounds, which has led to scientific investigation of their therapeutic properties. For example, tart cherries contain a phytochemical called cyanidin that demonstrates comparable anti-inflammatory activities to the NSAIDs ibuprofen and naproxen. Like NSAIDs, cyanidin in tart cherries inhibits COX enzymes, but without the side effects of NSAIDs. (Source)

Consumption of tart cherry juice prior to exercise has been found to relieve post-exercise muscle pain and accelerate exercise recovery. Tart cherries also improve mobility and relieve pain in individuals with knee osteoarthritis. Tart cherries can be supplemented either as tart cherry juice or as an encapsulated tart cherry extract. (Source, Source, Source)

3. Ginger

Ginger comes from the rhizome of Zingiber officinale, an herbaceous plant native to Southeast Asia. Ginger has been used for hundreds of years in traditional Chinese medicine and Indian Ayurvedic medicine for relieving pain, inflammation, and digestive system complaints. (Source)

In individuals with rheumatoid arthritis, ginger supplementation increases anti-inflammatory gene expression and decreases pain. Ginger also demonstrates broad anti-inflammatory activity and pain-relieving effects on a par with ibuprofen for pain caused by dysmenorrhea (period cramps), post-surgical pain, and knee osteoarthritis. (Source, Source, Source, Source, Source)

One of the main active constituents of ginger with anti-inflammatory activity is gingerol. Like NSAIDs, gingerol decreases inflammation by inhibiting COX enzyme expression. However, rather than harming the gastrointestinal tract, ginger offers gastrointestinal-protective properties. (Source)  

Ginger is typically consumed as a tea or in the form of powdered root in capsules. Please note that ginger tea and capsules can be irritating if you have acid reflux, so consult with your health care provider before trying ginger tea or ginger capsules.

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4. Curcumin

Curcumin, a brilliant yellow substance found in turmeric root, has been used for thousands of years in traditional Chinese and Indian medicine for its potent anti-inflammatory and antioxidant properties. In recent years, scientific research has validated the traditional uses of curcumin, causing it to hit the mainstream.

Curcumin inhibits multiple inflammatory cytokines and signaling pathways involved in pain and autoimmunity, including TNF-α, IL-1β, and NF-κB activity. In fact, research indicates that curcumin is about as effective for alleviating arthritis pain as the NSAID diclofenac. It also significantly reduces inflammatory biomarkers, including C-reactive protein and ESR (erythrocyte sedimentation rate) in individuals with rheumatoid arthritis and ulcerative colitis. (Source, Source, Source)

Finally, a large systematic review and meta-analysis of 31 randomized controlled trials found that curcumin and turmeric extract (which contains curcumin as a primary constituent) are clinically effective treatments for rheumatoid arthritis, psoriasis, and ulcerative colitis. (Source)

While you can get curcumin by eating turmeric root, it constitutes a meager 3.14% of the turmeric root, meaning you would need to eat very large amounts of turmeric to consume a clinically significant quantity of curcumin. Furthermore, curcumin is a hydrophobic compound, meaning it does not dissolve readily in water. These properties make curcumin poorly bioavailable when it is consumed as fresh or powdered turmeric root. Therefore, curcumin supplements provide the most bang for your buck if your goal is to alleviate aches and stiffness. When shopping for a curcumin supplement, look for patented forms of curcumin, such as Meriva® curcumin, which are formulated to be highly bioavailable. (Source)

5. Boswellia

Boswellia serrata, also known as Indian frankincense, is a time-honored herb that has been used in Indian Ayurvedic medicine for millennia. In recent years, scientific research has confirmed the potent anti-inflammatory and pain-relieving properties of boswellia extract.

Boswellia contains boswellic acids, which inhibit enzymes, transcription factors, and cytokines involved in inflammation. The lipoxygenase enzyme (LOX) is one of the primary inflammatory mediators inhibited by boswellic acids. Interestingly, while NSAIDs can disrupt the synthesis of glycosaminoglycan, a component of connective tissue, thus accelerating joint damage in arthritic conditions, boswellic acids have been shown to reduce glycosaminoglycan degradation. As a result, boswellia can not only alleviate pain and inflammation but may also help preserve connective tissue health. (Source, Source, Source)

Clinical trials indicate that boswellia can relieve pain and inflammation associated with knee osteoarthritis and rheumatoid arthritis. Boswellic acid, one of the bioactive compounds in boswellia, can reduce inflammation in inflammatory bowel disease. Interestingly, boswellia's anti-arthritic activity is enhanced when it is combined with curcumin. (Source, Source, Source, Source)

6. Fish Oil

Omega-3 fatty acids are essential fatty acids that our bodies cannot make, so we must consume them in our diets. Fish oil is particularly rich in omega-3 fatty acids. The primary omega-3 fatty acids found in fish oil are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).

Similar to NSAIDs, omega-3 fatty acids inhibit the production of pro-inflammatory prostaglandins. However, unlike NSAIDs, omega-3 fatty acids also boost the body’s production of anti-inflammatory signaling molecules. Due to their anti-inflammatory properties, omega-3 fatty acids may aid in the treatment of a variety of autoimmune diseases, including rheumatoid arthritis, lupus, and multiple sclerosis. (Source, Source)

The optimal dosage of fish oil for alleviating inflammation and pain hasn’t yet been determined. However, studies demonstrating the efficacy of fish oil for pain and inflammation typically use dosages of at least 2 g of EPA and DHA per day. (Source)

The Bottom Line on Natural Alternatives to NSAIDs

While there’s a time and place for NSAIDs, excessive use of these medications may compromise your health. Natural alternatives to NSAIDs can alleviate pain and inflammation and support the autoimmune disease healing process, without the side effects of NSAIDs.