Turmeric

1. Turmeric A presentation by Jason Thornton, CC Integrated Studies Student in Health Promotion, Nutrition, Psychology @ Weber State University

2. My interest in turmeric • I love food! • Curry is delicious. • I am very interested in Indian culture. • Its not manufactured in a lab. • I thought it would be easier to research and explain than a pharmaceutical drug without having a background in science… which turned out not to be the case!

3. Major themes • Botanical Information about Turmeric • Ayurveda and Turmeric • Chemical Structure of Curcumin • Western Science and Curcumin • Safety and dosage of Curcumin • Potential uses for Curcumin • Efficacy and Ethics Involved in Marketing Curcumin for therapeutic purposes • Conclusion • What you should know for the exam

4. Curcuma longa • Rhizomatous herbaceous perennial plant from the ginger family (zingiberales) • There are more than 120 Curcumaplants identified • Native to tropical South Asia • USDA Plant Hardiness Zone 11 • Cultivated predominately in China, Bengal, and Java • Grown in moist, warm soils rich in organic matter • Produce flowers in spring and re-bloom in summer through fall.

5. Turmeric flowers

6. Curry • Rhizomes, or tubers, of Curcuma longa are dehydrated and ground to a fine powder • Turmeric gives curry it’s golden color • Is known as Indian Saffron because of its colorant properties • Turmeric is made of: • ~5% essential oils • ~3-5% curcumin • A polyphenol that gives turmeric its color • Often used as a pH indicator • Yellow in acidic solutions (pH <7.4) • Bright red in basic solutions (pH>8.6)

7. Traditional uses for turmeric • In Asia, it is estimated that turmeric has been used for more than 2000 years of food preparation, cosmetics, fabric dying and medicine. (www.naturalstandard.com) • Used in wedding and religious ceremonies in India. • Introduced to Europe in the 13th Century by Marco Polo.

8. Ayurveda and turmeric

9. Clinical studies of curcumin • Apart from an early study published in The Lancet in 1937, curcumin/turmeric has only entered extensive preclinical studies and scientific phase I and II/III clinical trial levels in the last 10-15 years. • Literature review in March of 2011 yielded 12,032 hits • 54 references were of clinical trials • 1,016 references in a form of review • 1,408 references on patent applications (Basnet 2011)

10. Dosage and Side effects • Small doses of turmeric (curcumin) are taken daily as a spice by the population in many Asian cultures • Est. consumption of Indians of curcumin is 80-200 mg per day • Most studies conducted dosed between 500 to 1000 mg, 1-3 times daily.(White, 2011) • 12,000 mg daily have been given in experimental settings without significant adverse events. • Minor gastrointestinal side effects, including nausea and diarrhea, have been reported. (White, 2011) • There have been few reports of allergic dermatitis (Basnet 2011) • People with gallbladder disease should avoid supplementing turmeric (nccam.nih.gov) • GRAS by US FDA and has been demonstrated as atoxic in several studies

11. Chemical Structure • Curcumin is the principal curcuminoid of turmeric. • Desmethoxycurcumin (curcumin II) and bisdesmethoxycurcumin (curcumin III) are two other curcuminoids found in turmeric • Curcuminoids are natural phenols, responsible for the yellow color of turmeric. • As a food additive it is known as E100 or Natural Yellow 3 • Also used as a food preservative • 1,7-bis(4-hydroxy-3-methoxyphenyl)

12. Mechanisms of action • Curcumin is often cited as pleiotropic, meaning it has the ability to interact with many cell targets. • Accumulating experimental evidence suggests that curcumin interferes with a variety of molecular targets and processes involved in cancer • Curcumin possesses diverse pharmacologic effects including: • anti-inflammatory • anti-oxidant, • anti-proliferative and • anti-angiogenic activities • In cancer cells, curcumin exerts anti-inflammatory and growth-inhibition by inhibiting expression of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha. (Taylor, 2011)

13. Mechanisms of action Bisht, S., & Maitra, A. (2009). Systemic delivery of curcumin: 21st century solutions for an ancient conundrum. Current Drug Discovery Technologies, 6(3), 192-199. • The clinical advancement of this promising molecule has been hindered by: • poor water solubility • short biological half-life • low bioavailability after oral administration • A variety of approaches are being pursued to overcome these limitations, which include synthesis of curcumin analogues, the use of adjuvants (e.g. glycerol or ethanol), and the development of improved delivery platforms for the parental compound, including liposomal, nanoparticulated and phospholipid complex formulations of curcumin. • Much of the research today is focused on how to make curcumin more bioavailable.

14. Polyphenols: a review • Polyphenols in the human diet are derived mainly from vegetables, fruits and spices. • Coffee, green and black tea, chocolate, red wine, olive oil, and nuts are some examples of good sources of polyphenols. • Many of these polyphenol-rich natural resources have been traditionally used as medicines for the prevention of diseases, as well as maintenance of youth and longevity. • Recent line of studies has confirmed that these traditionally used natural remedies are strong antioxidant and anti-inflammatory agents. • Many polyphenols play important roles in regulating the immune system either acting alone or in combinations (Basnet 2011)

15. Polyphenols • http://www.nutraingredients.com/Research/Veteran-researcher-Polyphenols-don-t-work-as-antioxidants-in-vivo-but

16. Inflammation and cancer

17. Inflammation and cancer • Inflammation process is the essential part of the body physiology since acute inflammation is needed for the prevention from pathogens. • Chronic inflammation is a low level inflammation that can persist over 20 to 30 years- eventually leading to cancer as well as other chronic diseases. • Pro-inflammatory factors might be external such as environmental pollutants, viruses, bacteria, food, stress, etc. • Several immune cells and their products guide and connect the inflammation reaction to the cancer progression. • Principal target molecules of internal pro-inflammatory factors reponsible for mediating the inflammation are the free radicals, interleukins, tumor necrosis factor, nuclear factor and NSAID-activated gene-1. • Alhough these molecules are essential for normal cell regulation processes, uncontrolled and too high exposure to such molecules can lead to chronic disease..

18. Cancer-cure Potential • The anti-oxidative and anti-inflammatory properties of curcumin mightprovide a therapeutic window for the treatment of cancer. • Curcumin down regulates various pro-inflammatorycytokine expressions such as tumor necrosis factor (TNF-α), interleukins (IL-1, IL-2, IL-6, IL-8, IL-12) and chemokines, most likely through inactivation of the nuclear transcription factor, nuclear factor (NF)-κB. Likewise, curcumin is known to decrease the inflammation associated with experimental colitis, including a substantial reduction of the rise in myleoperoxidase (MPO) activity, an established marker for inflammatory cells (mainly polymorphonuclear leukocytes) and TNF-α. • In addition, curcumin is able to reduce colonic nitrite levels and down regulate cyclooxygenase (COX)-2,inducible nitric oxide synthase (iNOS) expression and p38 mitogen activated protein kinase (MAPK) activation [6,7]. • In spite of the abundant evidence at the molecular level, and extensive studies at the preclinical and clinical levels, its therapeutic outcome remains a challenge owing to its low solubility and poor bioavailability. (Basnet 2011)

19. Rheumatoid arthritis Deodhar, S., Sethi, R., & Srimal, R. (1980). Preliminary studies on antirheumatic activity of curcumin (diferuloyl methane). Indian J Med. • This very small (N=18) double-blind crossover study showed a statistically significant improvement in morning stiffness, walking time, and joint swelling in RA patients taking curcumin

20. psoriasis Heng, M. C., Song, M. K., Harker, J. and Heng, M. K. (2000) Drug-induced suppression of phosphorylase kinase activity correlates with resolution of psoriasis as assessed by clinical, histological and immunohistochemical parameters. Br J Dermatol. 143, 937-949. • A cohort study demonstrated that curcumin applied topically in a gel formulation to patients with psoriasis resulted in either resolution or reduction in psoriatic plaques after 8 weeks of treatment.

21. Irritable Bowel Disease • Two studies have found curcumin to have a positive effect on patients with IBS. • A cohort study (N=10) of patients with ulcerative colitis or Crohn’s disease demonstrated symptomatic improvement after consuming curcumin for 2 and 3 months respectively. (Holt, 2005) • A randomized, double-blind, multicenter trial (N=89) showed that 6 months of daily curcumin improved the clinical activity index and maintained remission in patients with ulcerative colitis. (Hanai, 2006) • Authors of these studies conclude that larger-scale, double-blind trials need to be conducted to establish a role for curcumin in the treatment of ulcerative colitis (Taylor, 2011)

22. Inflammatory eye diseases Lal, B., Kapoor, A., Asthana, O, et al. (1999) Efficacy of curcumin in the management of chronic anterior uveitis. Phytother Res. 13: 318-322 Lal, B., Kapoor, A., Agrawal P., et al. (2000) Role of curcumin in idiopathic inflammatory orbital pseudotumours. Phytother Res. 14: 443-447. • A cohort study (N=32) found that curcumin was as effective as corticosteroids for chronic anterior uveitis. (Lal, 1999) • Another cohort study (N=5) showed that curcumin reduced or resolved inflammatory orbital pseudotumor. (Lal, 2000)

23. Kidney Transplantation • A cohort study followed 43 dialysis-dependent cadaver kidney recipients who had taken curcumin for 1 month. Investigators observed reduced acute rejection and neurotoxicity over the course of 6 months (Shoskes, 2005)

24. obesity • In a study of high-fat-fed rats, curcumin effectively reduced the elevated serum and hepatic triglycerides. (Manjunatha, 2006) • In a study of high-fat-fed hamsters, curcumin was effective at lowering the triglycerides and free fatty acids in their plasma. (Jang, 2008) • In vitro and in vivo studies in high-fat-fed mice demonstrated that curcumin supplementation (500mg/kg diet) can increase the basal metabolic rate, thereby contributing to increased energy expenditure and weight loss. (Ejaz, 2009) • Curcumin has also been shown to be beneficial in aiding glycemic control in diabetics, further enhancing its role in cardiovascular disorders. (Alappat, 2010)

25. What science bodies are saying • The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health states that “little reliable evidence exists to support the use of turmeric for any health condition because few clinical trials have been conducted. • While preliminary findings from animal and laboratory studies suggest that curcumin may have anti-inflammatory, anticancer, and antioxidant properties, these findings have not been confirmed in people. • NCCAM continues to fund basic research studies on the potential role of turmeric in preventing acute respiratory distress syndrome, liver cancer, and post-menopausal osteoporosis. (nccam.nih.gov)

26. Curcumin supplements Health Claims: Curcumin is the major component of Turmeric (Curcuma longa L.) and extensive scientific research on Curcumin has demonstrated its potent antioxidant properties. Through its antioxidant mechanisms, Curcumin supports colon health, exerts neuroprotective activity and helps maintain a healthy cardiovascular system.* Powerful Antioxidant From Turmeric Root Extract Helps Maintain Cardiovascular Health Maintains Healthy Joints* Vegetarian Formula

27. Curcumin supplements Health Claims: The active ingredients in Curcuma longa are plant substances called curcuminoids compounds that demonstrate potent antioxidant properties in scientific studies. Curcuminoids may benefit the joints brain heart and the circulatory system by helping to neutralize free-radicals.

28. Curcumin supplements Health Claims: Inhibits Metabolic InflammationSupports Healthy Inflammatory Response Research shows turmeric root quenches metabolic inflammation by inhibiting the production of COX-2 enzyme. Source Naturals Turmeric Extract™ and Turmeric 1000™ provide support to the liver and its detoxifying properties, and have powerful antioxidant activity. Turmeric 1000™ provides a highly potent 1,000 mg per tablet of curcumin, the active ingredient. Turmeric is difficult to absorb, so BioPerine® and bromelain are added to enhance bioavailability.

29. At the end of the day… Extensive in vitro and animal subject research has been conducted and analyzed the effect of curcumin on: • Inhibition of lipozygenase • Cyclooxygenase-2 • Leukotrienes • Thromboxane • Prostaglandins • Tumor Necrosis Factor However, such extensive research is lacking on human subjects (White, 2011) Curcumin’seffectiveness is limited due to low water solubility, low biological half-life, and low bio-availability with oral administration.

30. What to know for the test • The plant family that turmeric is part of. • How much curcumin is found in turmeric. • Which curcuminoid is of most interest in clinical studies. • Why curcumin isn’t acknowledged by the NIH to be an effective pharmacological supplement. • The many uses of turmeric other than nutritional supplement. • Potential benefits curcumin has on the body. • Potential risks curcumin has on the body.