September 4, 2019

Curcumin with Turmeric Essential Oil for Knee Osteoarthritis

As effective as diclofenac, with superior tolerability
Randomized trial finds curcumin with turmeric essential oil is just as effective as diclofenac for the treatment of knee pain from osteoarthritis, with fewer adverse effects. The curcumin/turmeric combination could be a safe and effective NSAID alternative.

Reference

Shep D, Khanwelkar C, Gade P, Karad S. Safety and efficacy of curcumin versus diclofenac in knee osteoarthritis: a randomized open-label parallel-arm study. Trials. 2019;20(1):214.

Study Objective

To evaluate the safety and efficacy of curcumin compared to diclofenac for pain relief of knee osteoarthritis (OA).

Design

Prospective, randomized, open-label, parallel, active control clinical trial

Participants

The study included 139 patients aged 38-65 years old from the City Care Accident Hospital in Parli Vaijnath, Maharashtra, India. Participants had knee OA (confirmed by x-ray), with moderate pain, for at least 3 months. There were 70 (45 male, 25 female) patients in the curcumin group and 69 (48 male, 21 female) patients in the diclofenac group.

Intervention

Patients received 500 mg of curcumin with turmeric essential oil (BCM-95 Curcumin) 3 times per day (TID) or 50 mg of diclofenac (a nonsteroidal anti-inflammatory drug [NSAID]) 2 times per day (BID) for 28 days.

Study Parameters Assessed

The study parameters were assessed at baseline (day 0), week 2 (day 14), and week 4 (day 28). Parameters included the Visual Analog Scale (VAS) for Pain, Knee Injury and Osteoarthritis Outcome Score (KOOS), weight changes, antiflatulent effect, patient’s global assessment of symptom relief, physician’s global evaluation of treatment, and anti-ulcer effect.

Primary Outcome Measures

The primary outcome measure was perception of pain via change in VAS (0-10, 10 being worst).

Key Findings

Both treatment groups experienced a significant reduction (P<0.05) in pain level.

  • Average VAS scores at baseline were 7.84±0.63 (curcumin) and 7.81±0.73 (diclofenac).
  • At day 14, VAS scores were 4.69 ± 0.79 (curcumin) and 4.58 ± 0.60 (diclofenac).
  • At day 28, VAS scores were 2.20 ± 0.81 (curcumin) and 2.20 ± 0.61 (diclofenac).
  • A VAS reduction of >50% was achieved in 66/70 participants in the curcumin group and 67/69 participants in the diclofenac group.

A common adverse effect of NSAIDs is gastrointestinal (GI) upset. Nineteen participants (28%) in the diclofenac group needed a histamine-2 receptor antagonist (H2 blocker) medication to address gastric problems, while 0% of the curcumin group did. Patients in the curcumin group also experienced a significant reduction in flatulence and body weight.

Practice Implications

Knee OA is a major cause of disability in the United States and worldwide. The incidence of knee OA has more than doubled since the mid-20th century.1 An estimated 30 million US adults are currently affected by OA.2 While the development of OA is a multifactorial process, the rising incidence seems to be influenced by the increasing rates of obesity, sedentary lifestyle, comorbid conditions, and longer life expectancy.3

Conventional management strategies include pain and inflammation control using NSAIDs, opioids, antidepressants, intraarticular injections, and topical therapies.4 A recent study published in JAMA demonstrated that “treatment with opioids was not superior to treatment with nonopioid medications for improving pain-related function over 12 months.”5 The study was looking at chronic back pain and hip or knee OA pain.

Nonsteroidal anti-inflammatory drugs are among the most frequently used medications and are available over-the-counter (OTC) or by prescription. Diclofenac sodium is only available by prescription in the United States, but some countries offer a lower dosage as an OTC medication. Even though NSAIDs are widely used and easy to access, they have some serious adverse side effects, including ulcers, GI bleeding, acute or chronic renal failure, and cardiovascular complications.6

With 16,500 deaths from NSAID use documented annually, clearly other pain management strategies are necessary.

Diclofenac sodium is one of the most commonly used NSAIDs worldwide.6 Its primary mechanism of action is theorized to be the inhibition of prostaglandin synthesis via the cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) pathways.7 Prostaglandins play a major role in acute inflammation and its cardinal signals (pain, redness, swelling, and heat). However, prostaglandins have beneficial activity as well. They help protect the mucosa, especially in the stomach, by balancing gastric acid secretions and pH. Inhibiting prostaglandin function can lead to ulcer formation and other serious GI side effects.8

Consequently, the most common side effects of NSAIDs generally have to do with the GI system. Minor complaints such as dyspepsia, heartburn, and nausea tend to be the most reported. More serious GI complications can include mucosal destruction leading to ulcers and strictures.6 Concomitant treatment with other medications to manage GI effects, like H2 blockers and proton pump inhibitors, may be necessary when patients are undergoing treatment with NSAIDs. Nonsteroidal anti-inflammatory agents are also known to increase fluid retention, contributing to cardiovascular adverse effects. Fluid retention is also a significant factor in weight gain while using this class of medications.9

Given the considerable risk of adverse effects from NSAIDs, it is important to explore safe, effective, and natural alternatives for managing OA pain. Curcumin is especially well-suited for this application as it has an extraordinary amount of data to support its usage for numerous diseases, including arthritic conditions.

A 2012 clinical study demonstrated curcumin’s (BCM-95) non-inferiority to diclofenac sodium for rheumatoid arthritis.10 The 3-arm study featured curcumin monotherapy, diclofenac monotherapy, and a combination group. All groups experienced a reduction in the Disease Activity Score and the American College of Rheumatology criteria. The biggest improvements were seen in the curcumin group, which was statistically significant. Additionally, 14% of the diclofenac sodium group withdrew because of adverse effects.

There are many ways to enhance curcumin’s relatively poor absorption and bioavailability. The use of turmeric essential oil has been shown to help maintain serum curcumin levels greater than 200 ng/g for over 8 hours. Turmeric essential oil also has research-validated health benefits. Researchers have identified a key compound in turmeric essential oil, called aromatic-turmerone (ar-turmerone) that possesses its own analgesic properties.11 Ar-turmerone has been shown in vitro (breast cancer and microglial cells) to have COX-2 and matrix metalloproteinase (MMP)-9 inhibition through targeting nuclear factor (NF)-κB.12,13 Ar-turmerone has also been shown to have positive impacts on neural stem cell proliferation.14

With 16,500 deaths from NSAID use documented annually, clearly other pain management strategies are necessary.15 Curcumin with turmeric essential oil offers a safe and effective solution for OA. Curcumin offers gastroprotective effects, including anti-ulcer properties. A 2016 animal model demonstrated that curcumin protected rats from naproxen-induced ulcers in a dose-dependent fashion by increasing radical scavenging enzymes (superoxide dismutase, catalase, glutathione peroxidase) and prevention of lipid peroxidation.16

Limitations

Limitations of this study include its open-label design, lack of a placebo group, and short duration. A treatment period of 28 days may be insufficient to draw long-term conclusions. A double-blind study that is longer in duration and involves more participants should be considered.

Conclusions

Overall, curcumin with turmeric essential oil (BCM-95 Curcumin) dosed at 500 mg TID appears to have a similar efficacy profile as diclofenac sodium 50 mg BID for relief of knee pain from OA. Due to the GI side effects of diclofenac, 28 participants had to undergo the addition of an H2 blocker, vs none of the participants in the curcumin group. The curcumin group experienced fewer and less severe adverse effects (13% in the curcumin group vs 38% in the diclofenac group), demonstrating its superior safety profile. Curcumin with turmeric essential oil may offer a safe and effective alternative to knee OA treatment, especially in patients who are particularly vulnerable to the side effects of NSAIDs.

Conflict of Interest Disclosure

Cheryl Myers is the Chief of Scientific Affairs and Education for EuroMedica, a dietary supplement and natural medicine company that has the exclusive product families of CuraPro and Curaphen, which feature BCM-95 Curcumin.

Categorized Under

References

  1. Wallace IJ, Worthington S, Felson DT, et al. Knee osteoarthritis has doubled in prevalence since the mid-20th century. Proc Natl Acad Sci USA. 2017;114(35):9332-9336.
  2. Lawrence RC, Felson DT, Helmick CG, et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II. Arthritis Rheum. 2008;58(1):26-35.
  3. Jiang L, Tian W, Wang Y, et al. Body mass index and susceptibility to knee osteoarthritis: a systematic review and meta-analysis. Joint Bone Spine. 2012;79(3):291-297.
  4. Hochberg MC, Altman RD, April KT, et al. American College of Rheumatology 2012 recommendations for the uses of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthritis Care Res (Hoboken). 2012;64(4):465-474.
  5. Krebs EE, Gravely A, Nugent S, et al. Effect of opioid vs nonopioid medications on pain-related function in patients with chronic back pain or hip or knee osteoarthritis pain: the SPACE randomized clinical trial. JAMA. 2018;319(9):872-882.
  6. Harirforoosh S, Asghar W, Jamali F. Adverse effects of nonsteroidal anti-inflammatory drugs: an update of gastrointestinal, cardiovascular and renal complications. J Pharm Pharm Sci. 2013;16(5):821-847.
  7. Gan TJ. Diclofenac: an update on its mechanism of action and safety profile. Curr Med Res Opin. 2010;26(7):1715-1731.
  8. Ricciotti E, FitzGerald GA. Prostaglandins and Inflammation. Arterioscler Thromb Vasc Biol. 2011;31(5):986-1000.
  9. Knights KM, Mangoni AA, Miners JO. Non-selective nonsteroidal anti-inflammatory drugs and cardiovascular events: is aldosterone the silent partner in crime? Br J Clin Pharmacol. 2006;61(6):738-740
  10. Chandran B, Goel A. A randomized, pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis. Phytother Res. 2012 Nov;26(11):1719-1725.
  11. Chen Z, Quan L, Zhou H, et al. Screening of active fractions from Curcumin Longa Radix isolated by HPLC and GC-MC for promotion of blood circulation and relief of pain. J Enthnopharmacol. 2019;234:69-75.
  12. Park SY, Kim YH, Kim Y, Lee SJ. Aromatic-turmerone attenuates invasion and expression of MMP-9 and COX-2 through inhibition of NF-kB activation in TPA-induced breast cancer cells. J Cell Biochem. 2012;113(12):3653-3662.
  13. Park SY, Jin ML, Kim YH, Kim Y, Lee SJ. Anti-inflammatory effects of aromatic-turmerone through blocking of NF-kB, JNK, and p38 MAPK signaling pathways in amyloid β-stimulated microglia. Int Immunopharmacol. 2012;14(1):13-20.
  14. Hucklenbroich J, Klein R, Neumaier B, et al. Aromatic-turmerone induces neural stem cell proliferation in vitro and in vivo. Stem Cell Res Ther. 2014;5(4):100.
  15. Cryer B. NSAID-associated deaths: the rise and fall of NSAID-associated GI mortality. Am J Gastroenterol. 2005;100:1694-1695.
  16. Kim JH, Jin S, Kwon HJ, Kim BW. Curcumin blocks naproxen-induced gastric antral ulcerations through inhibition of lipid peroxidation and activation of enzymatic scavengers in rats. J Microbiol Biotechnol. 2016;28;26(8):1392-1397.