Can any supplements be used to reduce inflammation in people sensitive to NSAIDs such as ibuprofen, high-dose aspirin, or naproxen?

Answer:

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to reduce pain and swelling, but some individuals, especially those with an underlying airway disease (such as asthma) or those with a history of chronic hives, cannot take these medications due to NSAID-induced hypersensitivity reactions. Symptoms of these reactions may include shortness of breath, congestion, airway obstruction, skin wheals, swelling beneath the skin (angioedema), hives and, in some cases, anaphylaxis (Kowalski, Allergy Asthma Immunol Res 2015). Some people with NSAID-induced hypersensitivity react to only one NSAID; these individuals may be able to take other NSAIDs. However, other people with NSAID hypersensitivity react to multiple NSAIDs.

What causes NSAID-induced hypersensitivity?

There are essentially two main types of hypersensitivity to NSAIDs. The first, which is least common, is an allergic reaction to a specific NSAID and possibly chemically similar NSAIDs. These patients may tolerate other NSAIDs that are not chemically similar. Most NSAID-induced hypersensitivity reactions, however, are not allergic reactions but relate to sensitivity associated with inhibition of cyclooxygenase-1 (COX-1), which is a common property of many NSAIDs. This type of hypersensitivity is cross-reactive, meaning that these individuals may react to more than one NSAID, even ones that are not chemically similar. Although most of these individuals may tolerate NSAIDs that target cyclooxygenase-2 (COX-2), some may react to these more specific NSAIDs as well (Kowalski, Allergy Asthma Immunol Res 2015).

Can supplements help people sensitive to NSAIDs?

Below we describe supplements commonly used for pain and/or inflammation. The first group would not seem to trigger NSAID sensitivity, however, and unfortunately, none have been shown to be as effective as NSAIDs. Supplements in the second group could potentially trigger NSAID sensitivity.

Supplements used for pain and/or inflammation that don't appear to trigger NSAID sensitivity:

Fish oil

Many uses of fish oil relate to its anti-inflammatory effects. Fish oil contains fatty acids that interact with cyclooxygenases (COXs). However, unlike NSAIDs, which inhibit the activity of COX-1 and/or COX-2, fish oil is converted by COX enzymes into molecules that reduce inflammation (Ye, Front Cardiovasc Med 2018). Based on its anti-inflammatory activity, fish oil has shown benefit for inflammatory conditions such as gout, ulcerative colitis, menstrual cramps, lupus, and others. However, unlike NSAIDs, which are fast-acting, fish oil may take several weeks before benefit is observed.

GLA (gamma-linolenic acid)

GLA, as found in evening primrose, has been used in treating inflammatory conditions such as rheumatoid arthritis, eczema, dry eye syndrome, and others, but clinical evidence supporting most of these uses is weak or lacking. In the body, GLA is converted to dihomo-gamma linolenic acid (DGLA), which can bind to COX enzymes and be converted to anti-inflammatory metabolites. However, DGLA can also be converted to arachidonic acid, which binds to COX enzymes and is converted to pro-inflammatory metabolites. These conflicting actions may partially explain the weak evidence of benefit of GLA for improving inflammatory conditions.

MSM (methylsulfonylmethane)

MSM has been used for treating pain associated with osteoarthritis, as well as conditions such as rheumatoid arthritis and inflammation of the bladder wall (interstitial cystitis), although its effectiveness hasn't been well established. The mechanism by which MSM may work isn't well understood, although it is known to contribute sulfur to the body, which can then be used to synthesize certain amino acids (building blocks for proteins), and it can act as an antioxidant.

Boswellia

Boswellia resin and extracts have shown benefit in reducing symptoms of inflammatory conditions such as osteoarthritis and ulcerative colitis. Boswellia resin contains compounds called boswellic acids, which are thought to have anti-inflammatory properties. Laboratory research has shown that boswellic acids, particularly the boswellic acid AKBA, reduce inflammation by inhibiting 5-lipoxygenase (5-LOX), a key enzyme in the biosynthesis of leukotrienes, which are compounds that cause inflammation. Be aware that the amount of boswellic acid in a boswellia supplement can differ depending on the form of boswellia used (i.e., resin or extract). Also, the absorption of boswellic acid can be affected by the supplement formulation (see the ConsumerTips section of our Joint Supplements Review for more details).

Arnica

Arnica is a plant that contains sesquiterpene lactones. These compounds are thought to reduce the activation of NF-kappaB, a protein complex within cells that controls certain genes involved in inflammation (Monaco, Proc Natl Acad Sci U S A 2004). While probably not a problem for people with NSAID sensitivity, there is not enough information to conclude that topical arnica is effective for any particular use, including pain or inflammation.

Supplements that may help with pain and/or inflammation but could potentially trigger NSAID sensitivity:

White willow bark

White willow bark contains salicin, a precursor to salicylic acid (the active metabolite of aspirin), which works as both a COX-1 and COX-2 inhibitor (Wu, Circulation 2000). Despite its long history of use, there have been only a few clinical studies evaluating white willow bark extract for inflammatory conditions such as osteoarthritis, and evidence has been mixed. Furthermore, because white willow bark works similarly to aspirin, people sensitive to aspirin may also be sensitive to white willow bark.

Turmeric

Many uses of turmeric relate to the anti-inflammatory activities of its constituent, curcumin. Curcumin from turmeric has been shown to be helpful for inflammatory conditions such as ulcerative colitis, rheumatoid arthritis and osteoarthritis. The anti-inflammatory action might involve blocking COX-2, similar to NSAIDs such as celecoxib. By targeting COX-2 and not COX-1, turmeric might be suitable option for some people with NSAID-induced hypersensitivity, but it is possible that others may react to this supplement.

Ginger

Ginger is a spice that has been shown to modestly reduce pain and disability in people with knee and hip osteoarthritis, although it does not seem to reduce pain associated with migraine headache. Phenolic compounds in ginger (gingerols and shogaols) have anti-inflammatory properties that may be responsible for some of ginger's effects. These compounds have been shown in laboratory studies to inhibit COX-2 activity, but not COX-1 activity (van Breemen, Fitoterapia 2011). Theoretically, this may make it unsuitable for some people sensitive to NSAIDs. Also, many ginger products do not contain the expected amounts of the active constituents. In fact, among 15 ginger products that ConsumerLab.com tested in 2020, six of the seven products that could not be approved contained unusually low amounts of gingerols and shogaols (see What CL Found for details).

SAMe (S-adenosyl-methionine)

SAMe is an effective option for reducing pain and inflammation association with osteoarthritis. It seems to work about as well as anti-inflammatory drugs and, although it may take longer to work, the effects seem to last longer. The mechanism by which SAMe reduces inflammation is not entirely clear, although it may involve inhibition of COXs (similar to NSAIDs). Theoretically, this may make it unsuitable for people sensitive to NSAIDs, although we are unaware of any reported cases of cross-reaction. Be aware that people taking antidepressants such as MAO inhibitors, SSRIs, and tricyclics should use SAMe only if advised to do so by their doctor, and those taking levodopa should be aware that SAMe might reduce the effectiveness of this drug (see Concerns and Cautions for details).