turmeric and osteoarthritis cover

Turmeric and osteoarthritis

case presentation

A healthy, 55-year-old man presents with a 1-year history of bilateral knee discomfort.  He mostly gets mild stiffness in the mornings, pain with stairs and pain after getting up from a seated position.  He did have plain radiographs showing mild patellofemoral degenerative changes.  The patient has interest in alternative medicines due to his wife suffering a GI bleed from NSAIDs.  His friend told him about turmeric.  Which of the following options best describes turmeric?

A. Works to decrease COX-2, prostaglandins, and leukotrienes
B. Works to increase 5-HT receptors
C. Does not have a clear mechanism of action
D. Works to increase Na-K-2Cl receptors

introduction

Although many sports medicine providers do prefer to deal with sports injuries, a good portion of

practices involve managing patients with osteoarthritis (OA). There is a very high societal

cost that comes with OA and the management can vary among providers and patient

expectations and preferences may also be different.

With no approved disease-modifying drugs available for knee OA, current pharmacological

treatment options are limited to analgesics, intra-articular injectates such as corticosteroids,

PRP, viscosupplementation, stem cells, and non-steroid anti-inflammatory drugs (NSAIDs) [1].

While these medications have only a mild-to-moderate effect size for pain relief, they are

associated with gastrointestinal, renal, and cardiovascular complications and are often

contraindicated in patients with comorbidities [2].

The global demand for a safe and effective therapeutic option for OA have refocused the

interest from conventional drugs to complementary and alternative medicines. This post serves

to discuss the up to date data for using turmeric to treat osteoarthritis.

Curcuma longa (turmeric) is a spice commonly used in curry powders. Turmeric is a more

generalized name for a yellow powder that has been widely used as a homology as food and

medicine. The pharmacologically active constituent is curcumin, a pigment that gives the yellow

color to some mustards, broth, and other foods. Curcumin appears to have anti-inflammatory

effects because of inhibition of COX-2, prostaglandins, and leukotrienes [3]. Curcumin has

been deemed “generally recognized as safe” by the US Food and Drug Administration [4].

Prior to 2010, there was fairly limited data evaluating turmeric for the treatment of OA. Since

then, more trials have been occurring. One recent systematic review included sixteen different

randomized trials and included more than 1800 patients [2]. Eleven studies compared turmeric

extract formulations with and five studies were a head-to-head comparison between turmeric

extract and NSAIDs (either ibuprofen or diclofenac).

In the eleven studies compared to placebo and five compared to NSAIDs, turmeric extract had a

large effect on knee pain compared to placebo but a similar effect to NSAIDs. This was shown

using the VAS or WOMAC scores for the knee. Physical function was also evaluated clinically

and turmeric was also shown to have a significant effect on improving knee function compared

to placebo. It was also found to be comparable to NSIADs in regards to knee function.

All medications have risks of adverse events (AEs) and side effects.  Turmeric generally carries a fairly favorable profile in regard to both.  In one systematic review, there were no severe AEs recorded and those reported were non-specific with gastrointestinal discomfort secondary to nausea, diarrhea and dyspepsia being most prevalent. Among the studies comparing turmeric to placebo, five studies displayed no significant difference in AEs. One study identified a dose dependent rise in AEs in the turmeric groups [6].  Another study showed high dose turmeric therapy had a significant increase in AEs while low dose therapy displayed no significant changes when compared to placebo. Other studies have shown a similar or decreased effect when compared to NSAIDs [5].

Figure 1.  Forest Plot showing summary of turmeric studies on knee pain.   Adopted from [2].

Studies have shown curcumin can inhibit platelet-activating factor and arachidonic acid platelet aggregation. Due to its anti-thrombotic effects, concomitant use of turmeric with other drugs with similar pharmacological potential such as naproxen may increase the risk of bleeding, and therapy modification is recommended [7].  Several pre-clinical studies have investigated interactions between curcumin and drugs. One such study in mouse models of acute nociceptive pain demonstrated a synergistic interaction in combination with pregabalin.  Others have reported increased side effects with tacrolimus and the possibility of decreasing the effectiveness of certain chemotherapy agents [7].

Another challenging variable when evaluating turmeric and osteoarthritis is the variability in formulations and dosing.  In a systematic review, all studies used a different formulation (ie, Turmacin, Meriva, Theracurcumin, Curene) that modified the pharmacokinetics of turmeric in order to increase bioavailability. Dosing of the turmeric therapies varied from 93 mg per day to 2 g per day. There is no standardized scale to compare the different preparations [5].

Figure 2.  Summary of turemric studies for knee function.  Adopted from [2].

Manufacturers are working to make turmeric more “bioavailable” for many reasons.  One particular named “BCM-95” formulation is composed of curcuminoids and essential oil of turmeric containing turmerones. Combination of curcuminoids with turmerones (essential oil components of turmeric) has been reported as a powerful tool in the prevention of inflammation and related symptoms.  One of the studies with this particular formulation showed noninferiority in more than 140 patients with paracetamol [8].

Summary

In summary, turmeric formulations to treat osteoarthritis have shown promise.  This has particularly increased in the past fifteen years.  Almost all studies have shown that turmeric has the ability to decrease inflammation and increase function.  There is significant variability in the formulations and dosing and standardization of these things needs further investigation.

CASE CONCLUSION

Curcuma longa (turmeric) is a spice commonly used in curry powders. Turmeric is a more generalized name for a yellow powder that has been widely used as a homology as food and medicine. The pharmacologically active constituent is curcumin, a pigment that gives the yellow color to some mustards, broth, and other foods. Curcumin appears to have anti-inflammatory effects because of inhibition of COX-2, prostaglandins, and leukotrienes.  It does not work to increase 5-HT receptors or increase Na-K-2Cl receptors.

References

  1. Bannuru RR, Osani MC, Vaysbrot EE, et al. OARSI guidelines for the non-surgical

management of knee, hip, and polyarticular osteoarthritis. Osteoarthr Cartil.

2019;27:1578-1589.

  1. Wang, Zhiqiang, et al. "Efficacy and safety of turmeric extracts for the treatment of knee

osteoarthritis: a systematic review and meta-analysis of randomised controlled

trials; Current Rheumatology Reports 23.2 (2021): 1-11.

  1. Natural Medicines Comprehensive Database. 8th ed. Stockton, Calif.: Therapeutic

Research Faculty, 2006. http://www.naturaldatabase.com. Accessed August 23, 2007.

  1. Gupta SC, Sung B, Kim JH, et al. Multitargeting by turmeric, the golden spice: From

kitchen to clinic. Mol Nutr Food Res. 2013;57(9):1510-1528.

  1. Paultre, Kristopher, et al. “Therapeutic effects of turmeric or curcumin extract on pain and function for individuals with knee osteoarthritis: a systematic review.” BMJ open sport & exercise medicine 7.1 (2021): e000935.
  2. Henrotin Y, Malaise M, Wittoek R, et al. Bio-optimized Curcuma longa extract is efficient on knee osteoarthritis pain: a double-blind multicenter randomized placebo controlled three-arm study. Arthritis Res Ther 2019;21:179.
  3. Keihanian, F.; Saeidinia, A.; Bagheri, R.K.; Johnston, T.P.; Sahebkar, A. Curcumin, Hemostasis, Thrombosis, and Coagulation. J. Cell Physiol. 2018, 233, 4497–4511. 

8. Singhal, Shubha, et al. “Bioavailable turmeric extract for knee osteoarthritis: a randomized, non-inferiority trial versus paracetamol.” Trials 22 (2021): 1-11.