Turmeric (Curcuma longa) as an Anti-Inflammatory for Arthritis

April 2000; Volume 3; 44-47

By Teresa Klepser, PharmD, and Nicole Nisly, MD

Arthritis is a disabling disease. more than 10% of persons over the age 65 suffer from rheumatoid arthritis (RA), and millions more from osteoarthritis (OA). Common symptoms include morning stiffness, generalized malaise, and painful joints. Inflammatory synovitis, joint deformities, muscle spasms, bone and cartilage destruction, and/or vasculitic lesions are common.

Conventional therapies include non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and slow-acting antirheumatic drugs (e.g., gold, methotrexate, and hydroxychloroquine), especially for RA. Dietary supplements have also been widely used, and those thought to provide benefit for arthritis include ginger, glucosamine, chondroitin, and turmeric.

Turmeric is a member of the ginger (Zingiberaceae) family that grows in tropical Asian countries and India.1 The rhizome is the part of the plant of medical importance and is responsible for the yellow-orange color of the spice called turmeric.1 Harvested at the end of the growing season, turmeric is sun-dried prior to use.2

Reported Uses

Turmeric has many reported uses including management of gastrointestinal problems such as peptic ulcers, appetite stimulation, flatulence, abdominal bloating, hepatitis, upper abdominal pains, colic, and diarrhea.1-4 Among natives of Thailand and India turmeric is believed to be useful for the treatment of dizziness and gonorrhea and is commonly used as a tonic, blood purifier, antispasmodic, and digestive aid.1 When applied topically, turmeric may be used to treat insect bites, ringworm, infected wounds, bleeding, and inflammation of the oral mucosa.1,2

Reported Indications

Turmeric has been approved by the German Commission E for the treatment of liver and gallbladder disorders and for loss of appetite.2

Constituents

Turmeric contains a wide variety of bioactive compounds, including volatile oil, curcuminoids, and 1,5-diaryl-penta-1,4-dien-3-on- derivatives. The volatile oil, which is 4-14% of the plant, consists of alpha- and beta-tumerone, artumerone, alpha- and gamma-atlantone, curlone, zingiberene, and curcumol.5 The volatile oil is believed to give choleretic action (stimulation of bile production).6

The curcuminoids curcumin, demethoxycurcumin, and bidemethoxycurcumin make up 3-6% of the plant.2,5 Curcumin gives turmeric its typical yellow-orange color.3 It is believed that curcumin is the major active component that possesses anti-inflammatory properties.4,6

Curcumin is poorly absorbed when orally administered.6 In rats, curcumin was excreted 38-75% in the feces.7 The fraction of curcumin that is absorbed undergoes hepatic metabolism and subsequent excretion in the bile.7 Curcumin is thought to demonstrate a local effect in the gastrointestinal tract and the systemic effects of the gallbladder at relatively low concentrations.6

Mechanism of Action

Curcumin has been demonstrated to exhibit anti-inflammatory activity in vitro and in vivo. Anti-inflammatory effects include arachidonic acid pathway enzyme modification, diminished neutrophil responses, stabilization of inflammatory cell membranes, and inhibition of platelet aggregation.8,9 The volatile oil has been reported to stimulate the adrenohypophyseal axis activity.10

Laboratory and Animal Studies

Arora et al evaluated the anti-inflammatory effects of turmeric extract, two of its constituents (fractions A and B), and hydrocortisone vs. control using four different rat models of inflammation.11 Using a cotton pellet method, researchers found that fractions A and B were almost as active as hydrocortisone; however, the extract was less effective. In a formaline-arthritic model, significant reduction of edema was observed with the extract, fractionated compounds, and hydrocortisone. According to a granuloma pouch method, the extract, fractions A and B, and hydrocortisone all reduced exudate formation among the rats. Lastly, using an adjuvant arthritis method, phenylbutazone was also injected in the rats. In this model, the inhibition of inflammation was significantly better with fraction A and phenylbutazone vs. hydrocortisone.

Clinical Studies

Few clinical studies have been published that demonstrate the benefits of turmeric among patients with arthritis. Although turmeric has also been suggested for use in OA, there are no published trials evaluating its efficacy in this setting.

In a randomized, double-blind, crossover study, Deodhar et al evaluated the effects of curcumin (400 mg tid) vs. phenylbutazone (Butazolin®) (100 mg tid for two weeks) in 18 patients with RA.12 All anti-inflammatory agents were discontinued four days prior to study initiation. Endpoints included duration of morning stiffness, fatigue time, time required to walk 25 ft, articular index of joint tenderness, grip strength of both hands, overall general improvement by the observer and by the patient, and side effects.

Both agents demonstrated statistically significant subjective improvement in morning stiffness, walking time, and joint swelling; however, there were no improvements in any of the objective measurements noted. Both agents resulted in significant overall general improvement as determined by an observer; however, only phenylbutazone resulted in overall patient-
perceived improvement.

Study limitations include small sample size, lack of a placebo group, and the absence of an interanalysis between turmeric and phenylbutazone. Because of its poor adverse effect profile, phenylbutazone was removed from the U.S. market by Geigy Pharmaceuticals as newer, better-tolerated NSAIDs became available.13

Adverse Effects

Stomach complaints, such as heartburn or ulcers, can occur following extended use or overdose.2 Curcumin has been reported to induce abnormalities in liver function tests in rats.15

Sharp, transient hypotensive effects have been noted to occur in dogs following curcumin administration.7 This effect has yet to be reported in man.

CNS effects potentially linked to curcumin include mild, transient giddiness.14

There are two cases of turmeric-induced allergic contact dermatitis in the literature.16,17 The first, a 64-year-old Indian male who developed subacute dermatitis of the hands, forearms, and dorsa of the feet after working as a miller in a spice shop.16 Allergy testing revealed a positive test result for Curcuma longa rhizome powder. This subject’s dermatitis improved following administration of systemic and topical steroids. The second case involved a 31-year-old female who suffered from erythema on the dorsa of her hands following self-medication with Chuu-ou-kou.17 Following the use of Chuu-ou-kou her lesions worsened and the patient developed edematous erythema, papules, vesicles, and itching on her hands. Allergy testing resulted in a positive test for Curcuma longa, the main ingredient in Chuu-ou-kou.

Which of the following has been reported as a side effect?

a. Giddiness

b. Increased menstrual flow

c. Agitation

d. Blurry vision

e. Headache


Contraindications/Precautions

Medicinal doses of curcumin may act as a strong gastrointestinal irritant.18 Turmeric should not be used in patients with bile duct obstructions or gallstones.1,4 Caution should be used among patients with hyperacidity or irritable stomachs. In medicinal doses, turmeric should not be used in pregnancy, since higher doses may stimulate menstrual flow and the uterus; however, it is generally regarded as safe in pregnancy and lactation when used as a spice.4 The safety of turmeric use as a medicinal during lactation is not known.4

Which of the following conditions is considered a contraindication for the use of turmeric?

a. Impotence

b. Gallstones

c. Migraines

d. Renal insufficiency

e. Congestive heart failure


Drug Interactions

No drug interactions have been reported in the literature.1 However, turmeric may possess anticoagulation properties via its inhibition of thromboxane A2, B2, or both. Therefore, turmeric may increase the risk of bleeding among patients taking anticoagulants such as warfarin or antiplatelet drugs such as aspirin or other NSAIDs.4,9,19

Since some of the active ingredients of turmeric are hepatically metabolized, caution should be exercised when using concurrently with agents that are metabolized via the cytochrome P450 system.

Dosage

There are a variety of recommended preparations and dosages. Turmeric is available as a tincture, tea, or capsules.2 The tincture (1:10) dosage is 10-15 drops two to three times daily.2,4 Teas are not recommended, as the volatile oil and curcuminoids are fairly water insoluble.6 Some capsules are formulated to give a standardized dose of 400-600 mg curcumin.5 The average daily dose is 1.5-3 g of turmeric powder divided into two or three doses taken between meals.2,4 (See Table 1.)


Table 1-Turmeric formulation and price comparison
Manufacturer Formulation Manufacturer's Recommended Dose Price/Quantity
Nutritional Dynamics Each capsule contains 400 mg turmeric rhizome 1 capsule/d $17.45/60 capsules
(Curcuma longa) standardized 95% curcumin
Nature's Herbs Each capsule contains 400 mg turmeric extract 1 capsule 2-3 times/d $15.49/60 capsules
Turmeric Power standardized to 95% curcumin in an herbal base with water
of turmeric
Nature's Herbs Each preservative-free capsule contains 300 mg 1 capsule 2-3 times/d $15.49/60 capsules
Curcumin Power certified potency turmeric extract concentrate with water
standardized for a minimum of preferred 95%
curcumins in a synergistic base of whole turmeric
powder
Cardiovascular Each capsule contains 80 mg curcumin from 1-2 capsules/d $13.95/60 capsules
Research Ltd. turmeric,10 mg zingerone-gingerol compound,
1,500 mcg saffron (Crocus sativus)
Source: Online mail-order companies



Since curcumin demonstrates poor absorption, it is often sold in combination with bromelain to enhance its absorption. The benefit of this combination has not been evaluated.5Topically, no typical dose is suggested in the literature.

Conclusion

Traditionally and historically, turmeric has been used in the treatment of inflammation, especially arthritis. Laboratory and animal data offer mechanistic support. Clinical data to support its use for this indication, however, are weak, though side effects appear to be rare.

Recommendation

Turmeric would not be considered a first-line agent for the treatment of arthritis given its contraindications and precautions, the potential for drug interactions, and the little clinical evidence. However, systemic side effects should be minimal.

Which of the following drugs may interact with turmeric?

a. Bromocriptine

b. Warfarin

c. Medroxyprogesterone

d. Penicillin

e. Probenecid


Dr. Klepser is Assistant Professor, University of Iowa College of Pharmacy, Division of Clinical and Administrative Pharmacy, and Dr. Nisly is Assistant Professor, University of Iowa College of Medicine, Department of Internal Medicine in Iowa City, IA.

References

1. Foster S. 101 Medicinal Herbs. Loveland, CO: Interweave Press; 1998.

2. Curcuma domestica. In: PDR for Herbal Medicines. Montvale, NJ: Medical Economics Company; 1998.

3. Leung AY. Better Health with (Mostly) Chinese Herbs & Food. Glen Rock, NJ: AYSL Corporation; 1995.

4. Natural Medicines Comprehensive Database [database online]. Stockton, CA: Therapeutic Research Center, Inc.; 1999.

5. The Natural Pharmacist [database online]. Roseville, CA: Prima Communications, Inc; 1999.

6. Robbers JE, Tyler VE. Tyler’s Herbs of Choice. Binghamton, NY: The Haworth Herbal Press, Inc.; 1999.

7. Ammon HP, Wahl MA. Pharmacology of Curcuma longa. Planta Med 1991;57:1-7.

8. Ammon HP, et al. Mechanism of anti-inflammatory actions of curcumine and boswellic acids. J Ethnopharmacol 1993;38:113-119.

9. Srivastava KC, et al. Curcumin, a major component of food spice turmeric (Curcuma longa) inhibits aggregation and alters eicosanoid metabolism in human blood platelets. Prostaglandins Leukot Essent Fatty Acids 1995;52:223-227.

10. Chandra D, Gupta SS. Anti-inflammatory and anti-arthritic activity of volatile oil of Curcuma longa (Haldi). Indian J Med Res 1972;60:138.

11. Arora RB, et al. Anti-inflammatory studies on Curcuma longa (turmeric). Indian J Med Res 1971;59:1289-1295.

12. Deodhar SD, et al. Preliminary study on antirheumatic activity of curcumin (diferuloyl methane). Indian J Med Res 1980;71:632-634.

13. Phenylbutazone. In: Drugdex. Englewood, CO: MICROMEDEX; 1999.

14. Satoskar RR, et al. Evaluation of anti-inflammatory property of curcumin (diferuloyl methane) in patients with postoperative inflammation. Int J Clin Pharmacol Ther Toxicol 1986;24:651-654.

15. Kiso Y, et al. Antihepatotoxic principles of Curcuma longa rhizome. Planta Med 1983;49:185-187.

16. Goh CL, Ng SK. Allergic contact dermatitis to Curcuma longa (turmeric). Contact Dermatitis 1987;17:186.

17. Hata M, et al. Allergic contact dermatitis from curcumin (turmeric). Contact Dermatitis 1997;36:107-108.

18. Diseases of the Liver and Biliary Tract. In: Weiss RF, ed. Herbal Medicine. Beaconsfield, England: Beaconsfield Publishers Ltd.; 1998.

19. Shah BH, et al. Inhibitory effect of curcumin, a food spice from turmeric, on platelet-activating factor and arachidonic acid-mediated platelet aggregation through inhibition of thromboxane formation and Ca2+ signaling. Biochem Pharmacol 1999;58:1167-1172.