Osteoarthritis (OA) impacts over 30 million Americans, with joint pain and musculoskeletal pain in general being one of the top reasons people see their physicians.1 Accompanying signs of arthritis are altered joint alignment, lack of joint mobility, morning stiffness, joint swelling, joint line tenderness, bony enlargements and pain with exercise in some cases.1,2 First-line therapies for OA include patient education, over the counter analgesics (acetaminophen) and anti-inflammatories (NSAIDs), a walking or light exercise program, weight management or nutrition program, and a referral to a physical therapist or chiropractor to help with symptom management.1

Redefining Osteoarthritis

When most clinicians think of OA, what comes to mind is a disease of “wear and tear.” We consider what we were taught during our training, which is to focus on the loss of joint space and a degradation of cartilage. We now know that OA is much more involved than what we learned in medical school even 10 years ago. OA really should be referred to as “whole joint failure,” just as loss of full function on the heart is diagnosed as heart failure and loss of full function of the kidney is diagnosed as renal failure. Whole joint failure involves not only the cartilage but also helps us take into consideration the underlying bone, synovial membrane, synovial fluid, tendons, muscles, nerves, nociceptor sensitivity and underlying metabolic factors (TIMP/MMP activity).2

Traditional Osteoarthritis Therapies

Traditional therapies target primarily 5-LOX, COX-1, COX-2, and PLA2 inflammatory pathways via oral medication or intraarticular injection to provide pain relief. However, this relief comes at a cost of more cartilage loss than previously thought and higher risks. Safer treatment alternatives should be a primary consideration, given the constraints of NSAIDs, especially in those with high cardiovascular risk, gastrointestinal and renal comorbidities, and the constraints of acetaminophen in those with high risk of liver injury or multiple medication adverse reactions.

In fact, a recent study at Boston University School of Medicine found accelerated arthritis and joint destruction can be the unintended result of intra-articular corticosteroid injections.3 Safe and effective alternatives can be taken long-term with no side effects, given the chronicity of OA. Further, considering the need for pain, metabolic and “whole joint” structural benefits, turmeric—an ancient, golden spice—is the gold standard for first-line and long-term OA therapy.

Benefits of Turmeric for Osteoarthritis Therapy

The phytochemical analysis of turmeric has revealed that there are 200-plus bioactive molecules present in the natural matrix of turmeric that contribute to its health benefits. The main constituents are the curcuminoids, which include curcumin, demethoxy curcumin and bis-demethoxy curcumin. In addition to this, the non-curcuminoid components, like turmerin, turmerones, elemene, furanodiene, curdione, bisacurone, cyclocurcumin, calebin A, and germacrone,4-7 all have shown the ability to reduce pain and inflammation separate from curcumin.8,9,12-16 The broad-spectrum bioactives mechanistically go above and beyond the primary targets traditional therapies.

Recently, scientists have discovered that the microbiome metabolizes these bioactives and they enhance the anti-inflammatory signaling capacity of turmeric’s bioactives. Studies show turmeric’s bioactives increase microbiome diversity, inhibit and protect the body from LPS-induced inflammation,10 fortify enterocyte tight junctions and increase afferent vagus nerve signaling.11 These mechanisms provide a range of benefits that truly match the mechanistic needs of arthritic joints beyond a wear-and-tear or local inflammatory approach.

In vitro and in vivo studies indicate that the entire spectrum of bioactives in turmeric exhibits antioxidant, antineoplastic, antiviral, antiarthritic, anti-amyloid and anti-inflammatory properties. But just how does the golden therapy stack up in clinical trials? Multiple double-blind, placebo-controlled clinical trials of osteoarthritis and rheumatoid arthritis patients have shown a decrease in pain, increase in joint function, and improved inflammatory and autoimmune biomarkers, and turmeric has also outperformed NSAIDs in head-to-head trials.8,12-16

 

Helping physicians find patients who they can best help

 

A Turmeric Matrix and Osteoarthritis Case Study

In 2017, a double-blind, placebo-controlled, three-arm study using a turmeric matrix extract was performed with 36 active rheumatoid arthritis (RA) patients, conducted at the Indian Institute of Technology and published in the Journal of Medicinal Food. Patients were evaluated by doctors who adhered to the American College of Rheumatology criteria, which included physical exams as well as pain and function questionnaires. The patients also had baseline metabolic panels and inflammatory biomarkers measured (CRP, ESP and Rf) before and after the 90-day treatments. The active RA patients were randomly assigned to receive either a 250 mg x 2/per day dose, 500 mg x 2/day dose, or placebo (corn starch) dose.

The results showed safety and efficacy of both the low and high doses of the turmeric complex extract. The Disease Activity Score-28 (DAS28) saw a change of 52% for the low dose, 65% change for the high dose, and no change for placebo. The Visual Analog Scale (VAS) saw a 62% change for the low dose, 72% change for the high dose, and a 3% change in the placebo group. Overall both the DAS28 and VAS showed statistically significant improvements in scores with the higher dose resulting in greater improvement in scores. The ESR, CRP and Rf values of both low and high dose patient groups showed statistically significant improvements and a dose-response showing greater improvement with the higher dose. The ACR20 analyzed patients for the number of swollen joints, pain and physical function.

The Results

Once again, both groups showed improvements not only the number of total swollen joints but also a reduction in the severity of swelling and improvement in function in both high- and low-dose groups. Finally, results in pain, function, inflammatory and rheumatoid biomarkers began to improve by the end of the first month (data mentioned in study discussion but not published).

 

 
 


Educated in both the Netherlands and the United States, Dr. Adrian den Boer is a board-certified and licensed naturopathic and chiropractic physician. In addition, Dr. den Boer is fully certified as a functional medicine doctor. Dr. den Boer has treated over 10,000 patients successfully by utilizing multiple resources to manage patient care. Most recently, he joined the Lifestyle Matrix Resource Center as the Clinical Expert serving the MSK Solutions Pain Recovery Program.

 

 

References

1. Hunter, D. and Bierma-Zeinstra, S. (2019). Osteoarthritis. The Lancet, 393(10182), pp.1745-1759.
2. O’Neill, T. and Felson, D. (2018). Mechanisms of Osteoarthritis (OA) Pain. Current Osteoporosis Reports, 16(5), pp.611-616.
3. Andrew J. Kompel, Frank W. Roemer, Akira M. Murakami, Luis E. Diaz, Michel D. Crema, Ali Guermazi. Intra-articular Corticosteroid Injections in the Hip and Knee: Perhaps Not as Safe as We Thought? Radiology, 2019; 190341
4. Li S. Chemical Composition and Product Quality Control of Turmeric (Curcuma longa L.). Vol 52011.
5. edited by P.N. Ravindran KNB, Sivaraman K. Turmeric : the genus Curcuma. Boca Raton, FL : CRC Press. 2007.
6.  Amalraj A, Pius A, Gopi S, Gopi S. Biological activities of curcuminoids, other biomolecules from turmeric and their derivatives - A review. Journal of traditional and complementary medicine. 2016;7(2):205-233.
7. Agarwal S, Mishra R, Gupta AK, Gupta A. Chapter 5 - Turmeric: isolation and synthesis of important biological molecules. In: Tewari A, Tiwari S, eds. Synthesis of Medicinal Agents from Plants. Elsevier; 2018:105-125.
8. Kuptniratsaikul V, Dajpratham P, Taechaarpornkul W, et al. Efficacy and safety of Curcuma domestica extracts compared with ibuprofen in patients with knee osteoarthritis: a multicenter study. Clin Interv Aging. 2014;9:451-458.
9.  Behal R, Mali AM, Gilda SS, Paradkar AR. Evaluation of local drug-delivery system containing 2% whole turmeric gel used as an adjunct to scaling and root planing in chronic periodontitis: A clinical and microbiological study. J Indian Soc Periodontol. 2011;15(1):35-38.
10. 10. Ghosh SS, Bie J, Wang J, Ghosh S. Oral supplementation with non-absorbable antibiotics or curcumin attenuates western diet-induced atherosclerosis and glucose intolerance in LDLR-/- mice--role of intestinal permeability and macrophage activation. PLoS One. 2014;9(9):e108577.
11. Dou Y, Luo J, Wu X, et al. Curcumin attenuates collagen-induced inflammatory response through the "gut-brain axis". J Neuroinflammation. 2018;15(1):6.
12.  Amalraj A, Varma K, Jacob J, et al. A Novel Highly Bioavailable Curcumin Formulation Improves Symptoms and Diagnostic Indicators in Rheumatoid Arthritis Patients: A Randomized, Double-Blind, Placebo-Controlled, Two-Dose, Three-Arm, and Parallel-Group Study. J Med Food. 2017;20(10):1022-1030.
13. Kuptniratsaikul V, Thanakhumtorn S, Chinswangwatanakul P, Wattanamongkonsil L, Thamlikitkul V. Efficacy and safety of Curcuma domestica extracts in patients with knee osteoarthritis. J Altern Complement Med. 2009;15(8):891-897.
14. Jacob J, Amalraj A, Raj KKJ, Divya C, Kunnumakkara AB, Gopi S. A novel bioavailable hydrogenated curcuminoids formulation (CuroWhite) improves symptoms and diagnostic indicators in rheumatoid arthritis patients - A randomized, double blind and placebo controlled study. Journal of Traditional and Complementary Medicine. 2018.
15. Sterzi S, Giordani L, Morrone M, et al. The efficacy and safety of a combination of glucosamine hydrochloride, chondroitin sulfate and bio-curcumin with exercise in the treatment of knee osteoarthritis: a randomized, double-blind, placebo-controlled study. Eur J Phys Rehabil Med. 2016;52(3):321-330.
16. Amalraj A, Varma K, Jacob J, et al. A Novel Highly Bioavailable Curcumin Formulation Improves Symptoms and Diagnostic Indicators in Rheumatoid Arthritis Patients: A Randomized, Double-Blind, Placebo-Controlled, Two-Dose, Three-Arm, and Parallel-Group Study.  J Med Food. 2017;20(10):1022-1030.

 


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