Bioavailable Curcumin for Rheumatoid Arthritis

A randomized controlled trial

By Paul Richard Saunders, PhD, ND, DHANP, CCH

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Reference

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.

Objective

To determine the efficacy and safety of oral administration of 2 different doses of a novel curcumin formulation in patients with active rheumatoid arthritis (RA).

Design

Pilot study; randomized, double-blind, placebo-controlled three-arm trial.

Participants

Thirty-six individuals aged 22 to 55 years, 15 female and 22 male, with RA according to the 2010 revised American College of Rheumatology (ACR) criteria.

According to the ACR criteria, all participants were functional class II and had a disease activity score greater than 5.1, with the sum of their tender joint count and swollen joint count greater than 8 at screening and baseline. They had either a C-reactive protein (CRP) greater than 0.6 mg/dL or an erythrocyte sedimentation rate (ESR) greater than 28 mm/h. The presence of Sjögren syndrome or limited cutaneous vasculitis was permitted.

Unfortunately we are still left to weigh the benefits vs the costs on a long-term basis for the diverse forms of curcumin available in the market place.

Patients were excluded if they had RA requiring disease-modifying antirheumatic drugs (DMARDs), nonsteroidal antiinflammatory drugs (NSAIDs), significant secondary involvement of any systemic organ, inflammatory joint disease other than RA, other systemic autoimmune disorder, any surgical treatment within 12 weeks of baseline, or a surgery planned within 24 weeks of randomization into the trial. Also excluded were patients who used anti-inflammatory, antirheumatoid, analgesic, steroid, or other drugs that would in the opinion of the investigators interfere with the study for 4 weeks prior to the study, in the case of parenteral or intra-articular drugs, and 2 weeks prior, in the case of oral drugs, before enrollment and during the study.

Intervention

Patients were randomized to receive either 250 mg of curcumin extract twice a day, 500 mg of curcumin extract twice a day, or 500 mg of food grade starch twice a day as placebo, for 90 days. The turmeric product was composed of major components of the turmeric root. The supplement used (turmeric matrix) was recreated by recombining extracted curcuminoids (50%), turmeric essential oil (3.0%), protein (2.0%), total carbohydrate (40.0%), and dietary fiber (5.0%). The curcuminoids were extracted with ethanol, the essential oil was extracted by steam distillation, and the carbohydrate, fiber, and protein were extracted with water.

The study was done at the Dhanwantri Ayurvedic College Hospital and Research Centre, Siddapur, Karnataka, India. Three of the authors are employees of Aurea BioLabs Ltd, the maker of the supplements and a research subsidiary of Plant Lipids Ltd. The other authors report no conflicts.

Study Parameters Assessed

Total cholesterol, random serum glucose, creatine, sodium, potassium, urea, total bilirubin, total protein, albumin, alkaline phosphatase, CRP, ESR, rheumatoid factor (RF), disease activity score 28 (DAS28), visual analog scale (VAS), American College of Rheumatology 20 (ACR20), total swollen joints, and total tender joints.

Key Findings

There were no significant changes between baseline and end of visit or between the 3 treatments groups in the following measures: height, weight, BMI, total cholesterol, random glucose, creatine, sodium, potassium, urea, total bilirubin, total protein, albumin, and alkaline phosphatase.

Statistically significant changes in assessments compared to baseline include the following:

  • VAS improved in each group: low-dose, 62.5%; high-dose, 72.3%; placebo, 3.5%
  • DAS-28 improved in low-dose (52.6%) and high-dose (66%) groups but remained unchanged in the placebo group
  • ESR fell in each group: low-dose, 88.1%; high-dose, 88.6%; placebo, 29.6%
  • CRP fell in each group: low-dose, 29.9%; high-dose, 51.2%; placebo, 11.3%
  • RF fell in each group: low-dose, 80.2%; high-dose, 84.2%; placebo, 13.1%
  • ACR20 scores fell in the low-dose (70.3%) and high-dose (75.7%) groups but remained unchanged in the placebo group
  • Total swollen joints fell in each group: low-dose, 80.4%; high-dose, 84.8%; placebo, 3.7%
  • Total tender joints fell in each group: low-dose, 78.1%; high-dose, 88.0%; placebo, 4.4%

All improvements in assessments and reduction of inflammatory markers were statistically significant in both high-dose and low-dose treatment groups when compared to placebo (P≤0.001 for all except the low dose for total tender joints [P≤0.01]). Although the high-dose group had greater changes vs the low-dose group, they were not significantly greater.

To summarize, significant improvements were seen with both curcumin treatment doses in VAS, DAS-28, ESR, CRP, RF, ACR20, total swollen joints, and total tender joints at the end of 90 days. Any changes found in the placebo group were minimal and not statistically significant. The difference between changes in the high-dose group compared to the low-dose group were not statistically significant.

There were no adverse events observed or reported and both doses were well-tolerated.

Practice Implications

Curcumin is well-known to have therapeutic effects in cardiovascular, neurodegenerative, psychiatric (depression), pulmonary, metabolic, autoimmune, and neoplastic conditions.1,2 The principal issue has been absorption and finding a therapeutic dose that is manageable and does not cause nausea and diarrhea.3 Study doses have been as high as 12 g per day. The result has been a proliferation of products that claim to be more bioavailable than their competitors.4

A review of 7 forms of curcumin available in the marketplace revealed that a hydrophilic carrier dispersed curcuminoids slightly better than a curcuminoids cyclodextrin complex at 45.9 and 45.0 times more bioavailable, respectively, to 95% curcuminoids powder control.5 The product used in the present study was not part of that review and does not claim to be as bioavailable as the hydrophilic and cyclodextrin forms. One of the study products reviewed made a 65-fold greater bioavailable claim but methodological anomalies make their determination unclear.

In 2015, Gopi (one of the authors of the present study) et al did a single-dose bioequivalence study using 500 mg of the study reformulation, 500 mg of 95% curcumin unformulated, and placebo.6 Participants were 12 healthy males, aged 18 to 45 years, with BMIs of 18.5 to 30.0. The reformulated curcumin was 10 times more bioavailable than the unformulated 95% curcumin.

A systematic review and meta-analysis published in 2016 identified 10,293 publications, which were distilled to 8 randomized clinical trials of joint pain due to osteoarthritis and RA that were treated with curcumin.7 The authors concluded that curcumin could be used as a dietary adjunct to conventional therapy and supported the concept that a larger clinical trial could lead to its acceptance as a standard therapy for many forms of arthritis.

One of the positive features of the present study is not only the 2 dose regimens but also the 90-day trial period. Pain can take time to resolve, especially in RA, a condition that can wax and wane due to a variety of circumstances. It is important to let patients know approximately how long it may take for them to feel sustained improvement. Three months is not unreasonable in a chronic condition such as RA, especially since the inflammatory markers measured showed significant improvement at the end of this trial. Once pain has decreased, would the patient maintain their gain if we prescribed half the initial dose? Only time or a clinical trial will tell.

It is also important to know that the lower dose worked as effectively as the higher dose, statistically. If a lower dose is effective, the financial outlay for curcumin treatment should be less. It can be frustrating for physicians and patients to have a treatment that works but costs far more than the raw material because it is high-tech, making it out of range for the patient’s pocketbook. Unfortunately we are still left to weigh the benefits vs the costs on a long-term basis for the diverse forms of curcumin available in the market place.

Summary

Rheumatoid arthritis is an autoimmune disease that affects about 1% of the world’s population and more than 1.3 million Americans; RA is the third most common arthritis after osteoarthritis and gout,8 and research suggests that 1 in 28 women (3.6%) and 1 in 59 men (1.7%) in the United States will develop RA during their lifetime.9 Patients with RA typically have a 10-year to 15-year shorter lifespan due to the widespread inflammation that extends beyond joints, affecting many organ systems.8

The curcumin extract used in this 90-day trial when compared to placebo was statistically significant at both 250 mg twice per day and 500 mg twice per day. Significance was shown for VAS, DAS-28, ESR, CRP, RF, ACR20, total swollen joints, and total tender joints. There were no adverse events. While this product is worth considering in one’s practice, the larger questions remain: Which Curcuma longa extract or reformulation is most effective? What is the cost to our patients? How long will they have to take it? What dose is optimal for sustained long-term benefit?

About the Author

Paul Richard Saunders, PhD, ND, DHANP, CCH, completed his PhD in forest ecology at Duke University, his naturopathic degree at Canadian College of Naturopathic Medicine, and his homeopathic residency at National University of Naturopathic Medicine, where he also earned a second naturopathic degree. He is professor of materia medica and clinical medicine at the Canadian College of Naturopathic Medicine; senior naturopathic doctor, Beaumont Health System, Troy Hospital, Michigan; and adjunct professor of integrative medicine, Oakland University William Beaumont Medical School and has a private practice in Dundas, Ontario. Saunders was a member of the transition team that formed the Office of Natural Health Products, served as a natural health expert to the Directorate, and has served on several expert panels for Health Canada. He has conducted clinical research, supervised students and residents, and published widely.

References

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  2. Lopresti AL, Drummond. PD. Efficacy of curcumin, and a saffron/curcumin combination for the treatment of major depression: a randomised, double-blind, placebo-controlled study. J Affect Disord. 2017;207:188-196.
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  4. Prasad S, Tyagi AK, Aggarwal BB. Recent developments in delivery, bioavailability, absorption and metabolism of curcumin: the golden pigment from golden spice. Cancer Res Treat. 2014;46(1):12-18.
  5. Douglass BJ, Clouatre DL. Beyond yellow curry: assessing commercial curcumin absorption technologies. J Am Coll Nutr. 2014;34(4):347-358.
  6. Gopi S, George R, Thomas M, Jude S. A pilot cross-over study to assess the human bioavailability of “cureit” a bioavailable curcumin natural matrix. Asian J Pharm Technol Innov. 2015;3(11):92-96.
  7. Daily JW, Yang M, Park S. Efficacy of turmeric extracts and curcumin for alleviating the symptoms of joint arthritis: a systematic review and meta-analysis of randomized clinical trials. J Med Food. 2016;19(8):717-729.
  8. Rheumatoid Arthritis Support Network. Rheumatoid Arthritis Facts and Statistics. http://www.rheumatoidarthritis.org/ra/facts-and-statistics/. Updated August 3, 2016. Accessed April 9, 2018.
  9. Crowson CS, Matteson EL, Myasoedova E, et al. The lifetime risk of adult-onset rheumatoid arthritis and other inflammatory autoimmune rheumatic diseases. Arthritis Rheum. 2011;63(3):633-639.