Turmeric

Introduction

Turmeric and its recognized active component, curcumin, are mainly promoted for proposed anti-inflammatory and anti-oxidant properties.¹ These compounds have been studied and used for a variety of medical conditions, from cancer to general good health. Millions of dollars are spent each year on turmeric and curcumin supplements in North America.² This document will give an overview of turmeric and the evidence available for its use and safety.

Background

Turmeric is a plant in the ginger family that has been used in many parts of the world as a food, cosmetic, and medicine.⁸ It is the spice that gives curry powder and prepared mustard their yellow color.

As early as 1949, turmeric has been reported to have antibacterial activity.⁴ Over the years, turmeric has been studied as an anti-inflammatory, hypoglycemic, antioxidant, wound-healing agent, and antimicrobial agent. It has been used for protection against hepatic conditions, chronic arsenic exposure, alcohol intoxication, metabolic syndrome, indigestion, prevention of irritable bowel syndrome, osteoarthritis, Crohn’s disease, ulcerative colitis, rheumatoid arthritis, type-2 diabetes prevention in people with prediabetes, depression, general good health, cancer, etc.^4,5

What is Turmeric?

Turmeric generally contains 2% to 6% curcuminoids, the ingredients thought to be responsible for its medicinal properties.^4,6 There is wide variability in the amount of curcuminoids found in turmeric powder as well as in the different products found on the market.⁶ Curcuminoids are generally made up of about 80% curcumin, 18% demethoxycurcumin, and 2% bisdemethoxycurcumin.⁴

Turmeric is commercially available in many forms including tablets, capsules, ointments, and as an additive in energy drinks, soaps, cosmetics, etc.⁴ Turmeric products often contain an extract, standardized to 80% to 95% curcuminoids, typically containing 80% curcumin.⁷ Some labels will indicate the specific amounts of curcuminoids and/or curcumin contained in turmeric products.

How it Might Work

The main active component of turmeric is curcumin. Curcumin’s potential anti-inflammatory effects are thought to be due to the inhibition of cyclooxygenase-2 (COX-2), prostaglandins, leukotrienes, and other pro-inflammatory cytokines.⁸ Animal studies also suggest curcumin may have effects on tumor necrosis factor, apoptotic proteins, C-reactive protein, total cholesterol, creatinine, triglycerides, antioxidants, AST, and ALT.⁴

Very preliminary research and animal studies suggest that curcumin may have antioxidant, antibacterial, and immunostimulatory effects, and may have activity against human immunodeficiency virus (HIV) and Leishmania parasites.⁸

Curcumin’s apparent chemopreventative and growth inhibition against several tumor cell lines is thought to be due to a reduction in the activity of pro-carcinogenic eicosanoids.⁸

There are reported antithrombotic effects in vitro and in animal studies, thought to be from the inhibition of platelet-activating factor and arachidonic acid platelet aggregation, perhaps by affecting thromboxane synthesis.⁸

From animal models, potential effects in Alzheimer’s disease are thought to be from the disaggregation of amyloid beta and decreased brain levels of amyloid, plaque, and oxidized protein.⁸

Dietary vs Supplement

The most common dose of turmeric extract used in clinical trials in patients with osteoarthritis is 500 mg two to four times per day.⁸ Reaching these doses with turmeric from food sources would be very difficult.

One teaspoon of ground turmeric can weigh between 2 g and 3.5 g. The range of curcumin is generally 2% to 6%, so the amount of curcumin in one teaspoon of turmeric can range anywhere from 40 mg to 210 mg. A turmeric extract dose of 1 g would require between three and 18 teaspoons of dried turmeric powder, much more than you would get from using turmeric or curry powder in everyday cooking.

Turmeric has also been used as a dye and can stain hands and clothing. If patients are using turmeric powder they should use caution to avoid staining.

Bioavailability

The curcumin component of turmeric has poor oral bioavailability. It is poorly absorbed, quickly metabolized, and quickly eliminated.⁴ There have been many attempts to formulate products with improved bioavailability. Some of these special formulations can cost up to $1 per 500 mg capsule.

Curcumin is metabolized by glucuronidation and sulfation.⁸ Adjuvants that are thought to block these metabolic pathways have been used to improve the bioavailability of curcumin.⁴ Piperine is believed to inhibit the hepatic and intestinal glucuronidation of curcumin.⁴ It has been reported to increase the bioavailability of curcumin by 2,000%.⁴ Piperine is found in black pepper.⁹ Bioperine is a black pepper extract that contains piperine and is found in some turmeric supplements.¹⁰

Bromelain in another adjuvant used to increase the absorption of curcumin; however, there appears to be little evidence to support its use.⁸

Taking turmeric with food is thought to increase its absorption.⁸

Meriva is a turmeric product developed to improve the bioavailability of the curcumin component. It is a complex of turmeric extract and soy phospatidylcholine.^8,11 Meriva 1 g is considered equivalent to 200 mg of curcumin.^8,11

Efficacy

In vitro and animal studies indicate there may be a role for turmeric in various conditions listed previously.¹² However, clinical evidence for the efficacy of turmeric is preliminary and limited. The clinical studies available are generally small, of limited duration, and of low quality. The most promising evidence for the use of turmeric may be in patients with osteoarthritis.

There are some clinical trials that suggest turmeric extract 1 g to 2 g per day may be effective in reducing the symptoms of osteoarthritis, and perhaps reducing the use of analgesics.^7,8,11,13 However, many of the studies are not well controlled, do not have comparator groups, and are of short duration. There are two studies from the manufacturer of Meriva of three and eight months duration.^11,13 The three month study of 50 patients did not include a control group.¹³ The eight month study of 100 patients compared Meriva plus standard therapy to standard therapy alone. Standard therapy was determined by each patient’s provider.¹¹ Although these studies did show a statistically significant reduction in osteoarthritis symptoms, neither of these small studies was blinded or randomized.^11,13

One randomized, placebo-controlled, single blind trial in 120 patients compared four groups: turmeric extract 500 mg twice daily vs placebo vs glucosamine vs curcumin 500 mg twice daily plus glucosamine. After 42 days, they reported a statistically significant decrease in osteoarthritis symptoms (p<0.05) and a decrease in the use of acetaminophen (p<0.01) in patients on curcumin compared to placebo.¹⁴

Safety

Turmeric appears to be well tolerated with no significant adverse effects reported at usual oral doses (e.g., 1 g to 2 g/day of turmeric extract).⁸ The FDA classifies it as “generally recognized as safe” (GRAS).⁴ There have been some isolated reports of gastrointestinal adverse effects, including dyspepsia, diarrhea, gastroesophageal reflux, nausea, and vomiting.⁸

It is recommended that turmeric/curcumin-containing supplements be avoided in women who are pregnant or nursing.^1,5 Turmeric might stimulate menstrual flow and the uterus.⁸

Despite a lack of clinical evidence, some also suggest caution for patients who have (or with a history of) gallstones and biliary tract obstructions, stomach ulcers, bleeding disorders, and those taking blood thinners or medications for diabetes.^1,5,8 There are case reports and animal data that suggest turmeric may lower blood glucose levels and glycosylated hemoglobin in patients with diabetes, have an antiplatelet effect, and cause gall bladder contractions.⁸

Drug interactions

There are several theories for drug interactions with turmeric, some based on in vitro and animal data. However, there does not seem to be enough clinical evidence to suggest increased monitoring or avoidance of certain medications when a patient is taking curcumin supplements.

In vitro and animal data suggests that the curcumin component of turmeric may reduce cytochrome P450 (CYP) enzyme inactivation but it does not appear to induce CYP enzyme activity.⁸ A study was done to investigate curcumin’s effects on CYP enzymes in eight healthy adults. They concluded that it was unlikely there was any clinically significant inhibition of CYP2C9, a common CYP enzyme and the one the most likely to cause an interaction affecting warfarin.¹⁵

In vitro and animal data also suggest turmeric supplements (but not foods) may bind to iron, reducing its absorption.⁸

There has been some preliminary clinical evidence for an interaction between the turmeric component of curcumin and sulfasalazine.⁸ Eight healthy patients received one 2 g dose of curcumin and one 2 g dose of sulfasalazine. This combination resulted in a 3.2 times increase in sulfasalazine plasma levels. This interaction could theoretically increase the effects and adverse drug reactions of sulfasalazine.³

Conclusion

Turmeric is a popular supplement being widely used for many different conditions. It appears to be safe and well tolerated at doses of 1 g to 2 g per day (turmeric extract). Evidence to support its efficacy for the reduction of symptoms in patients with osteoarthritis is limited and generally of low quality [Evidence Level B; lower quality RCT].¹⁴ Encourage patients to use proven medical therapies as prescribed by their providers.

Levels of Evidence

In accordance with the trend towards Evidence-Based Medicine, we are citing the LEVEL OF EVIDENCE for the statements we publish.

Adapted from Siwek J, et al. How to write an evidence-based clinical review article. Am Fam Physician 2002;65:251-8.

Project Leader in preparation of this professional resource: Annette Murray, BScPharm

References

1. Health Canada. Monograph: curcumin. February 2016. http://webprod.hc-sc.gc.ca/nhpid-bdipsn/monoReq.do?id=74&lang=eng. (Accessed November 7, 2016).
2. Majeed S. The state of the curcumin market. December 2015. http://www.naturalproductsinsider.com/articles/2015/12/the-state-of-the-curcumin-market.aspx. (Accessed November 7, 2016).
3. Kusuhara H, Furuie H, Inano A, et al. Pharmacokinetic interaction study of sulphasalazine in healthy subjects and the impact of curcumin as an in vivo inhibitor of BCRP. Br J Pharmacol 2012;166:1793-803.
4. Gupta SC, Patchva S, Aggarwal BB. Therapeutic roles of curcumin: lessons learned from clinical trials. AAPS J 2013;15:195-218.
5. Beck L. How to add turmeric to your healthy diet. February 2015. http://www.theglobeandmail.com/life/health-and-fitness/ask-a-health-expert/how-to-add-turmeric-to-your-healthy-diet/article22766168/. (Accessed November 7, 2016).
6. Tayyem RF, Heath DD, Al-Delaimy WK, Rock CL. Curcumin content of turmeric and curry powders. Nutr Cancer 2006;55:126-31.
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;19:717-29.
8. Jellin JM, Gregory PJ, et al. Natural Medicines Comprehensive Database. http://www.naturaldatabase.com. (Accessed November 6, 2016).
9. Derosa G, Maffioli P, Sahebhar A. Piperine and its role in chronic diseases. Adv Exp Med Biol 2016;928:173-84.
10. Pure Encapsulations. Curcumin 500 with Bioprene. 2016. http://www.pureencapsulations.com/curcumin-500-with-bioperine.html. (Accessed November 7, 2016).
11. Belcaro G, Cesarone MR, Dugall M, et al. Efficacy and safety of Meriva. A curcumin-phosphatidylcholine complex, during extended administration in osteoarthritis patients. Altern Med Rev 2010;15:337-44.
12. Jurenka JS. Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research. Altern Med Rev 2009;14:141-53.
13. Belcaro G, Cesarone MR, Dugall M, et al. Product-evaluation registry of Meriva, a curcumin-phosphatidylcholine complex, for the complementary management of osteoarthritis. Panminerva Med 2010;52:55-62.
14. 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 [abstract]. Inflammopharmacology 2013;21:129-36.
15. Volak LP, Hanley MJ, Masse G, et al. Effect of a herbal extract containing curcumin and piperine on midazolam, flurbiprofen and paracetamol (acetaminophen) pharmacokinetics in healthy volunteers. Br J Clin Pharamcol 2013;75:450-62.

Cite this document as follows: Professional Resource, Turmeric. Pharmacist’s Letter/Prescriber’s Letter. December 2016.

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