Knee osteoarthritis is a common painful condition, affecting 20 million persons in the United States alone. Since there may be safety concerns with typical long-term analgesic therapies — whether acetaminophen, NSAIDs, or opioids — alternative treatments are of great interest. A pair of studies examined the safety and efficacy of turmeric, glucosamine, or mud-pack therapy, with some favorable results.
The rhizome, or root, of turmeric (Curcuma longa linn.) has long been used in traditional Asian medicine to treat gastrointestinal upset, arthritic pain, and other ailments. Some laboratory and animal research has demonstrated anti-inflammatory and antioxidant properties of turmeric and its constituent curcumin. Writing in the journal Inflammopharmacology, researchers at St. John’s Medical College, Bangalore, India report a trial to evaluate this herbal remedy for its safety and efficacy in the treatment of painful knee osteoarthritis (OA), alone or in combination with glucosamine sulphate [Madhu et al. 2012].
This was a 42-day randomized, single-blind, placebo-controlled trial involving 120 patients (37 males, 83 females) with primary knee OA. Subjects were randomized into 4 groups (n=30/group) to receive either (a) placebo (400 mg twice daily), (b) turmeric (500 mg twice daily), (c) glucosamine (750 mg twice daily), or (d) glucosamine + turmeric (at the same doses as groups b and c).
Efficacy was assessed on days 21 and 42, and the primary outcome measures were decreased severity of pain and improved function assessed by Visual Analog Scale (VAS, 100mm) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale, respectively. Clinical examination of the affected joint used a Clinician Global Impression Change (CGIC) scale.
Posttreatment scores following administration of turmeric using VAS, WOMAC, and CGIC at each clinical visit showed significant improvements (P<0.05) compared with placebo. Also, the turmeric-treated group showed a significant (P<0.01) decrease in the use of rescue medication, along with clinical and subjective improvement compared with placebo.
There were overall improvements in signs and symptoms of OA seen with glucosamine alone and in combination with turmeric, but these reportedly were not statistically significant. The authors noted that turmeric was well-tolerated and safe in all patients throughout the study period, and this should be considered as a useful treatment option for patients with primary painful knee OA.
In a second article, a team of Spanish researchers systematically reviewed all of the scientific studies assessing the effectiveness of mud-pack therapy on patients diagnosed with knee OA [Espejo-Antúnez et al. 2012]. Writing in the journal Rheumatology, they report having identified 115 publications and 20 of those studies were chosen for review based on the inclusion criteria. Those selected were randomized clinical trials, systematic reviews, or meta-analyses whose objective was to analyze the effect of mud-pack therapy on perceived pain, function, and quality of life, with a sample size of ≥20 subjects, published since year 2000, and showing conclusive results.
Of the included studies, 12 analyzed functionality, 17 perceived pain, 5 quality of life, and all showed significant improvements associated with mud-pack therapy for those 3 analyzed variables. The methodological quality of the studies was moderate, with some risk of bias (ie, factors that might skew results). The researchers concluded that mud-pack therapy might be considered as an alternative and effective therapy in the clinical management of knee OA; however, studies with better methodology are needed to prove its scope.
COMMENTARY: The study of turmeric for OA was actually conducted and reported earlier by the lead author, Madhu, as a doctoral dissertation [Madhu 2010, see link below to document]. The turmeric used was designated as NR-INF-02, a water extract of Curcuma longa linn. and Oil of Curcuma longa linn. containing standardized turmerones, which are the chief chemical constituent in the rhizomes.
Turmeric (Curcuma longa) is mainly known as a deep yellow colored herbal powder used in Indian cooking and sometimes has been described as a "super spice" with a long list of health benefits. Therapeutic turmeric extracts and tablets are commercially available, but whether they would have the same constituents and qualities as used in this research study is unknown.
Subjects in all 4 groups in the Madhu study started with moderate pain (mean ≈64mm on VAS) at baseline, and all showed significant improvement by 6 weeks (see Graph). Even the placebo group demonstrated a large 0.87 effect size (Cohen’s d) for pain reduction. However, the largest effect for pain reduction from baseline to day 42 — 71%, or d=2.40 — was with turmeric (ie, NRINFO2) alone. [Note: effect sizes were calculated by us from study data.]
Turmeric also had the largest effect size for pain reduction compared with placebo (d=1.37); however, surprisingly, the addition of glucosamine to turmeric was the least effective therapy for pain compared with placebo (d=0.34). This might be an artifact of relatively small samples sizes and inadequate statistical power, rather than a negative interaction between turmeric and glucosamine.
It also seems unexpected that glucosamine alone would have a relatively strong effect compared with placebo (d=0.81), since other research has not demonstrated this agent as having significant efficacy for OA pain. Whether these results strongly favoring turmeric for knee OA would persist during longer-term therapy and in larger groups is undetermined.
As for the second paper, the use of mud therapy to cure ailments is not common in the U.S.; although, since antiquity, the soil of the earth has been used to remedy all sorts of health problems. Many cultures throughout history have used mud baths to refresh, invigorate, and heal.
Therapeutic mud goes beyond mere common “garden variety” soil, and tends to be brown in color, warm to the touch, and with little or no smell. It is usually composed of a complex, biologically active mixture of both organic and inorganic substances. Therapeutic mud-pack is composed of 3 distinct compounds: clay and mineral salts, liquid from thermal water, and organic matter and bacteria — which may combine to exert beneficial physical, chemical, and thermal effects.
Some research has demonstrated that natural, mineral-rich, mud-pack therapy, applied frequently over a multi-week period, may help to relieve inflammation and slow progression of knee OA. Relief of pain and joint stiffness may be observed over a several month followup period. The treatment appears to be safe; however, long-term effectiveness, ease of accessing such therapy, and cost-benefit relationships need further elaboration.
REFERENCES:
> Espejo-Antúnez L, Cardero-Durán MA, Garrido-Ardila EM, et al. Clinical effectiveness of mud pack therapy in knee osteoarthritis. Rheumatology. 2012(Dec); online ahead of print [abstract here].
> Madhu K, Chanda K, Saji MJ. Safety and efficacy of Curcuma longa extract in the treatment of painful knee osteoarthritis: a randomized placebo-controlled trial. Inflammopharmacology. 2012(Dec), online ahead of print [abstract here].
> Madhu K. NR-Inf-02, Glucosamine Sulphate, and Combination of the Two in the Treatment of Painful Osteoarthritis: A Randomized, Single Blind, Placebo Controlled Trial [dissertation]. Rajiv Gandhi University of Health Sciences, Karnataka, Bangalore, India; 2010 [PDF document available here].
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6 comments:
So, we should advise patients with painful arthritis to spend a few weeks at a spa offering mud treatments and serving gobs of Indian food. Really?!
First of all, Dr. L., you, yourself, have written that pain studies with less than 50 persons per group tend to falsely skew results in favor of the intervention. So, that study of turmeric, with small group sizes, could be completely in error and needs to be replicated with larger groups sizes -- at the least.
Secondly, where are patients realistically supposed to find therapeutic mud? And, who will pay for it? Is there even a health insurance code for mud!?
Thank you, Virbius, you are a good critic. However, please don’t shoot the messenger here.
There is so much concern these days about potential harms of traditional pharmacologic treatments for pain that it is important to consider and report on complementary and alternative therapies (CAM). That doesn’t necessarily mean that I endorse or strongly recommend any of those.
I agree that the study of turmeric by Madhu needs replication in larger groups. A most puzzling outcome was that the turmeric+glucosamine combination was much less effective than either ingredient alone. And the fact that glucosamine alone had such favorable effects is inconsistent with other research.
However, a research problem might be exactly matching the turmeric formulation used in the study by Madhu. And, of course, if recommending turmeric for patients there would be doubts about which commercial product would be appropriate.
As for mud… most of the research involved frequent applications over days or weeks, which would be impractical for almost all patients. This is not something that can be used occasionally, and, at that, it offers symptomatic relief and is not curative of arthritis pain; so, the process would need to be repeated. I doubt that insurance plans would pay for it.
•[ii] Vilai Kuptniratsaikul, Sunee Thanakhumtorn, Pornsiri Chinswangwatanakul, Luksamee Wattanamongkonsil, Visanu Thamlikitkul. Efficacy and safety of Curcuma domestica extracts in patients with knee osteoarthritis. Int J Mol Med. 2010 May;25(5):729-34. PMID: 19678780
I believe that the cryptic comment above directs us to an interesting study of turmeric for arthritis pain [click here].
In summary: 52 and 55 patients were randomized to C. domestica [turmeric] extracts and ibuprofen groups, respectively. Baseline characteristics of the patients in both groups were not different. The mean scores of the aforementioned outcomes at weeks 0, 2, 4, and 6 were significantly improved when compared with the baseline values in both groups. There was no difference in those parameters between the patients receiving ibuprofen and C. domestica extracts, except pain on stairs (p = 0.016). No significant difference of adverse events between both groups was found (33.3% versus 44.2%, p = 0.36 in C. domestica extracts and ibuprofen groups, respectively).
CONCLUSIONS: C. domestica [turmeric] extracts seem to be similarly efficacious and safe as ibuprofen for the treatment of knee OA.
Dr. Leavitt: I read a review and I thought it was on Pain-topics that when glucosomine studies were reviewed to determine efficacy, it appeared studies with positive outcomes used crystalline glucosomine sulfate as opposed to the less expensive glucosomine chondrotin. When analyzed this way, glucosomine sulfate consistently showed positive outcomes. Another way of looking at any of these studies is a question of "what is the diagnosis." Is the diagnosis inflammation or is there a mechanical problem. Looking at inflammation of the knee as a physical therapy, I would same that many times the underlying problem is with inhibition/delayed firing patterns in the gluteal, quadriceps and hamstring muscles and treating the symptom (inflammation) rather than the cause would not yield very positive results. A study that supplemented a more mechanical intervention and included manual therapy interventions and then added a supplement like glucosomine sulphate or tumeric or mud would yield a much more interesting a valid study.
Thank you, Dr. Silver, for your suggestions. Glucosamine and chondroitin are two separate agents and, as far as I know, whether separately or combined in a single supplement they have demonstrated limited benefits only in subsets of patients with joint pain. Your proposed research approach certainly has merit, but it would add variables that would need to be carefully controlled, making the design and analysis somewhat complex.
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