Inflammation is deadly, yet inflammation is also life-saving.
Major news headlines tout that inflammation is an enemy to be banished. Many of us may remember the fiery Time magazine cover from 2004 that referred to inflammation as “the secret killer.” Some of the earliest documentation of inflammation has been found on Egyptian papyruses dating from around 3000 BC.1 The cardinal signs of inflammation, such as redness, swelling, heat and pain, were mentioned almost 3000 years later by the Roman medical writer Aulus Cornelius Celsus.2
Our bodies would not be able to heal, recover, repair, defend or even exist without inflammation. The issue is not the inflammatory response itself, but the inability to neutralize an acute inflammatory response. This can happen when the body lacks the proper nutrients or ideal conditions (sleep deprivation, high stress levels, chronic illness, etc.) to resolve acute inflammation, a situation that can lead to the subsequent development of unresolved, chronic inflammation. Sometimes I describe acute inflammation as a house fire to patients. Inflammation does, after all, come from the Latin inflammare, which means to ignite or to burn. It takes a coordinated effort to put the fire out, but sometimes, sparks or embers remain and can reignite the fire, or start another one in a completely new spot. That is how acute inflammation can seed chronic inflammation, even in places unrelated to the original acute inflammatory response.
Move away from non-steroidal anti-inflammatory drugs
Non-steroidal anti-inflammatory drugs (NSAIDs) are some of the top-selling over-the-counter (OTC) drugs out there.3 Why is this the case? Well, NSAIDs can work for pain and inflammation and because they are OTC, people generally believe they are safe. But NSAIDs have been shown to increase the relative risk of gastrointestinal (GI) bleeding at least three-fold, with some studies citing up to tenfold. An estimated 16,000 people die each year from medications in the NSAID family.4 The primary mechanism of NSAIDs is to reduce the synthesis of prostaglandins by inhibiting an enzyme, cyclooxygenase (COX), that forms prostaglandins from arachidonic acid. Depending on the NSAID, there can be COX-1 selectivity, COX-2 selectivity or a combination thereof.
Promote inflammation resolution
The term anti-inflammatory is thrown around quite a bit in the natural medicine world. Yes, it’s true, there are herbs, nutrients, vitamins and minerals that reduce inflammation, but their mechanisms of doing so typically differ from those of traditional OTC or prescription anti-inflammatories. Natural anti-inflammatories have multiple mechanisms of action and are perhaps more accurately termed inflammation resolvers. It’s important to note that anti-inflammatory is not synonymous with pro-resolution, which is why I prefer calling them inflammation resolvers. Generally, natural medicines don’t stop inflammation in its tracks; they work by reining in excessive inflammation, promoting the resolution of inflammation and reducing the likelihood of long-term damage from chronic inflammation. But, because the term is so commonly recognized, I will refer to the natural ingredients discussed in this article as anti-inflammatory.
Curcumin matches or outperforms NSAIDs in clinical studies
One of the most well-known herbal anti-inflammatories comes from the rhizome of the turmeric plant (Curcuma longa). Turmeric contains about two to five percent of an active constituent called curcumin. Curcumin has been the subject of more than 20,000 published studies, ranging from major depressive disorder, osteoarthritis, Alzheimer’s disease and then some (Fig. 1). While the love of money may be the root of all evil, chronic inflammation appears to be at the root of almost every chronic disease. Not only can curcumin downregulate many of the pro-inflammatory cytokines (IL-1β, IL-6 and TNF-alpha), it can also help increase anti-inflammatory cytokines and antioxidant defenses.
In a clinical trial on patients with osteoarthritis, researchers compared the effects of curcumin with turmeric essential oil (500mg twice per day) and paracetamol (650mg three times per day) for six weeks. At the study’s end, the curcumin group experienced significant improvements in their Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores for pain, stiffness and joint function. In the curcumin group, 18% of the participants had more than a 50% improvement and 3% had more than a 70% improvement in their WOMAC scores, whereas no one in the paracetamol group had more than a 20% improvement. Lastly, the curcumin group had a 37% reduction in their C-reactive protein (CRP) levels and a 74.8% reduction in TNF-alpha levels.5
In another head-to-head comparison versus an NSAID (diclofenac sodium), curcumin performed as well as or better than the drug. For four weeks, patients with knee osteoarthritis received either 500mg of curcumin with turmeric essential oil three times per day or 50 mg of diclofenac sodium twice per day. The curcumin and diclofenac groups had similar reductions in their knee injury and osteoarthritis outcome (KOOS) score at days 14 and 28. However, 28% of the group receiving diclofenac required an H2 blocker due to the gastrointestinal pain or acidity versus no one in the curcumin group.6
Curcumin with turmeric essential oil has more than 90 published studies, including 41 human clinical trials. Most of the clinical trials used 500 mg twice per day for conditions like osteoarthritis, rheumatoid arthritis, major depressive disorder and type 2 diabetes.
Synergistic effects with boswellia
A botanical that works synergistically with curcumin is boswellia, a genus of moderate to large trees native to places like India, the Middle East and Northern Africa. A certain species, Boswellia serrata, is one of the most revered and ancient medicines used in Ayurveda. Historically, it was used for a wide range of conditions, such as rheumatism, dysentery, cardiovascular disease, bronchitis, asthma and other, seemingly unrelated conditions. However, when modern research started to identify some of its key anti-inflammatory activities, it made sense why this eclectic group of conditions could be favorably impacted by boswellia.
Within boswellia, there is a family of constituents called boswellic acids. The most powerful boswellic acid is called acetyl-11-keto-beta-boswellic-acid (AKBA), which appears to be responsible for much of the medicinal activities. One of the key mechanisms responsible for boswellia’s anti-inflammatory activity is inhibition of a pro-inflammatory enzyme called 5-lipoxygenase (5-LOX).7 When the 5-LOX enzyme pathway is activated, arachidonic acid becomes metabolized into inflammatory leukotrienes. Excessive leukotriene production is implicated in gastrointestinal diseases, arthritis and other joint issues, and bronchial and asthmatic conditions, among others. The troubling part about the 5-LOX pathway is there aren’t a lot of natural or pharmaceutical substances that can rein in this type of inflammation. Some of the only medications that touch this type of inflammation are steroids, which of course can be life-saving in the short-term, but often come with a host of very dangerous side effects.8
A 2019 study on osteoarthritis demonstrated the safety of boswellia and curcumin, even when combined with an NSAID. The first group received curcumin, boswellia and NSAID (400mg of ibuprofen or 50mg of diclofenac sodium), group two received curcumin and group three received an NSAID only. The first group had the most significant reduction in pain on the visual analog scale (VAS). Whereas group three, which only received NSAIDs, had the smallest reduction in VAS score and the highest number of adverse events.9
Andrographis addresses MMPs
Andrographis (Andrographis paniculata) is another herb with a long history in Ayurveda. One of the key compounds in andrographis, called andrographolide, can be as effective as silymarin (from milk thistle) when it comes to protecting the liver from toxins.10 While one of my favorite uses for this herb is for liver health, it exhibits many other anti-inflammatory properties. One of its key properties for combating inflammation is through the activation of nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor that upregulates cellular defenses and boosts antioxidant defenses.11
When it comes to joint inflammation, andrographis can reduce the expression of, and damage from, matrix metalloproteinases (MMPs). Under normal conditions, MMPs are tightly regulated enzymes to regulate and remodel tissues and the extracellular matrix. With inflammation, chronic infection (hepatitis C, certain cancers, etc.) or genetic polymorphisms, the increased activity of MMPs can lead to more destructive tissue damage throughout the body.12 Andrographis has been shown to reduce the overexpression of MMPs by stopping the inflammatory cascade that can activate these enzymes.13
In a cellular study, treatment with andrographis was shown to reduce damage to nucleus pulposus cells, which could indicate a potential role for andrographis in the treatment of intervertebral disc degeneration (IDD). Andrographis was shown to mitigate proinflammatory cytokines and MMPs, which led to a reduction in nucleus pulposus apoptosis. While human research is needed to verify these results, this study helps move us in the right direction.14
Omega-3s and specialized pro-resolving mediators
Omega-3 fatty acids, often referred to as omega-3s, are a group of polyunsaturated fats generally derived from cold-water fish. These nutrients are considered essential as the human body is unable to make them from raw materials. Therefore, we need a consistent supply of omega-3s. One of the main reasons omega-3s are so important is because they serve as precursors to some of the most anti-inflammatory compounds the body makes, collectively called specialized pro-resolving mediators (SPMs). These SPMs, like resolvins, protectins and maresins, help attenuate the likelihood of acute inflammation becoming chronic inflammation. By initiating class switching from the production of pro-inflammatory lipid mediators (leukotrienes, prostaglandins) to anti-inflammatory and resolution-promoting actions, SPMs can exert their influence on a wide range of chronic conditions. These actions explain how omega-3s can be beneficial for rheumatoid arthritis, autoimmune diseases, Alzheimer’s disease, type 2 diabetes, cancer and then some.15
While non-steroidal anti-inflammatory drugs shut down production of pathways like cyclooxygenase-2 (COX-2), SPMs can directly influence the chemical mediators involved in inflammation and flip the switch that lights the path to resolution. But many people are deficient in omega-3s (about two thirds of adults), and therefore, the inflammation often shifts from acute to chronic, unresolved inflammation.16 As if rampant omega-3 deficiencies weren’t enough, NSAIDs have been shown to block the production of SPMs, leading us further from inflammation resolution.17
Build a protocol
So, what do we do with all this information? Let’s talk about protocol building. First, I generally have most patients with arthritis, back pain, acute injuries or any type of inflammatory condition on curcumin (500mg twice per day) and boswellia (500mg once or twice per day). The curcumin I recommend is enhanced with turmeric essential oil, which has been shown to increase absorption by 700%.18 For boswellia, I recommend at least 10% AKBA concentration, with less than 5% beta-boswellic acid, which can interfere with AKBA’s activity. For omega-3s, I opt for a North Atlantic salmon source with the omega-3s in their natural ratio and position, bound to phospholipids and with bioactive peptides. The phospholipids help protect the sensitive omega-3s from heat, light and oxidation. Because it’s in a tablet form, there’s no concern about rancidity, unlike with some conventional fish oils. Most patients will do well with one or two tablets daily.
A general, initial supplement protocol for inflammation
- Curcumin with turmeric essential oil: 500 mg, twice per day
- Boswellia with at least 10% AKBA: 500 mg, once or twice per day
- Andrographis standardized to 20% andrographolide: 400 mg, once or twice per day
- Omega-3s with phospholipids and peptides: 1 to 2 tablets per day
- Dosages are highly individualized and recommended for non-pregnant adults
LEXI LOCH, ND, is an author, educator and integrative medicine practitioner. With a passion for botanical medicine, dietary supplements and collaborative care, she integrates nature, science and intuition to cultivate vitality. For the past nine years, Loch has been a member of the Scientific Affairs and Education team at EuroPharma USA, maker of EuroMedica dietary supplements. Contact her via email at info@euromedicausa.com.
References
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- Bindu S, et al. Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: A current perspective. Biochem Pharacol. 2020;180:114147. PubMed. https://pubmed.ncbi.nlm.nih.gov/32653589/. Accessed May 8, 2024.
- Wiegand TJ. Nonsteroidal Anti-inflammatory Drug (NSAID) toxicity. Practice Essentials. Sept. 2023. MedScape. https://emedicine.medscape.com/article/816117-overview. Accessed May 8, 2024.
- Singal S, et al. Bioavailable turmeric extract for knee osteoarthritis: a randomized, non-inferiority trial versus paracetamol. Trials. 2021;22:105. PubMed. https://pubmed.ncbi.nlm.nih.gov/33516238/. Accessed May 8, 2024.
- Shep D, et al. Safety and efficacy of curcumin versus diclofenac in knee osteoarthritis: A randomized open-label parallel-arm study. Trials. 2019;20(1):214. PubMed. https://pubmed.ncbi.nlm.nih.gov/30975196/. Accessed May 8, 2024.
- Siddiqui MZ. Boswellia serrata, A potential antiinflammatory agent: An overview. Indian J Pharm Sci. 2011;73(3):255-261. PubMed. https://pubmed.ncbi.nlm.nih.gov/22457547/. Accessed May 8, 2024.
- Hedi H, Norbert G. 5-lipoxygenase pathway, dendritic cells and adaptive immunity. J Biomed Biotechnol. 2004;2004(2):99-105. PubMed. https://pubmed.ncbi.nlm.nih.gov/15240920/. Accessed May 8, 2024.
- Pinzon RT, Buwana F. Potential therapeutic effects of Curcuma longa extract in patients with osteoarthritis: A randomized, controlled trial. J Pharm Sci Res. 2019;11(11):3628-3633. https://www.jpsr.pharmainfo.in/Documents/Volumes/vol11issue11/jpsr11111914.pdf. Accessed May 10, 2024.
- Abdulaziz Bardi D, et al. Andrographis paniculata leaf extract prevents thioacetamide-induced liver cirrhosis in rats. PLoS One. 2014;9(10):e109424. PubMed. https://pubmed.ncbi.nlm.nih.gov/25280007/. Accessed May 8, 2024.
- Chen HW, et al. Induction of Nrf2-dependent antioxidation and protection against carbon tetrachloride-induced liver damage by andrographis herba (chuān xīn lián) ethanolic extract. J Tradit Complement Med. 2012;2(3):211-9. https://pubmed.ncbi.nlm.nih.gov/24716135/. Accessed May 8, 2024.
- Callazos J, et al. The effect of gender and genetic polymorphisms on matrix metalloprotease (MMP) and tissue inhibitor (TIMP) plasma levels in different infections and non-infections conditions. Clin Exp Immunol. 2015;182(2):213-219. NCBI. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4608511/. Accessed May 8, 2024.
- Tangyuenyong S, et al. Andrographolide exerts chondroprotective activity in equine cartilage explant and suppresses interleukin-1 β -induced MMP-2 expression in equine chondrocyte culture. Int Sch Res Notices. 2014;2014:464136. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4897368/. Accessed May 10, 2024.
- Zhang L, et al. Andrographolide mitigates IL-1b-induced human nucleus pulposus cells degeneration through the TLR4/MyD88/NF-kB signaling pathway. Mol Med Rep. 2018;18(6):5427-5436. PubMed. https://pubmed.ncbi.nlm.nih.gov/30365119/. Accessed May 8, 2024.
- Serhan CN, Petasis NA. Resolvins and protectins in inflammation-resolution. Chem Rev. 2011;111(10):5922-5943. PubMed. https://pubmed.ncbi.nlm.nih.gov/21766791/. Accessed May 8, 2024.
- Murphy RA, et al. Long-chain omega-3 fatty caid serum concentrations across life stages in the USA: An analysis of NHANES 2011-2012. BMJ Open. 2021;11(5):e043301. PubMed. https://pubmed.ncbi.nlm.nih.gov/33972333/. Accessed May 8, 2024.
- Markworth JF, et al. Human inflammatory and resolving lipid mediator responses to resistance exercise and ibuprofen treatment. Am J Physiol Regul Integr Comp Physiol. 2013;305(11):R1281-R1296. PubMed. https://pubmed.ncbi.nlm.nih.gov/24089379/. Accessed May 8, 2024.
- Antony B, et al. A pilot cross-over study to evaluate human oral bioavailability of BCM-95CG (Biocurcumax), a novel bioenhanced preparation of curcumin. Ind J Pharm Sci. 2008;70(4):445-449. PubMed. https://pubmed.ncbi.nlm.nih.gov/20046768/. Accessed May 8, 2024.