Health Benefits of Turmeric/Curcumin

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Laurence Thomas
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1 Health Benefits of Turmeric/Curcumin Shobha Ghosh, PhD, FAHA Professor of Medicine and Physiology Department of Internal Medicine

3 Target Disease Clinical Trials with Curcumin # Dose of Curcumin Findings Obesity 2 1 g/day for 4 weeks 500 mg/day for 12 weeks Metabolic syndrome 2 2 g/day for 12 weeks mg/day Diabetes 3 Meriva (200mg/day) for 4 weeks 200 mg/day for 9 months to pre-diabetics 500 mg/day for days Reduced IL-1β, IL-4, VGEF Reduced LDL and lipid peroxidation Reduced LDL, TG No effect Improved blood flow in skin and retina Prevention of diabetes development Reduction in oxidative status Fatty liver disease 2 Meriva (1 g/day) for 8 weeks 70 mg/day for 8 weeks Reduced BMI, waist circumference, and improved liver function Reduced liver fat, improved liver function Cancer 13 6g/day with docetaxel for 6 cycles 2g/day with radiotherapy Dose escalation up to 8 g/day with docetaxel Theracurmin (200 mg 8 g) with Gemcitabine Depression 6 2 g/day along with anti-depressives 500 mg/day Curcumin with Fluoxetine Arthritis 5 Theracurmin (150 mg/day) for 8 weeks Fexofytol (42 mg/day) for 3 months Meriva (200 mg/day) for 3-8 months Curcumin (500 mg/day) with diclofenac Reduced PSA in this resistant population Reduces radiation dermatitis (Breast cancer patients) Increased tolerance to docetaxel and reduced cancer (metastatic breast cancer) Plasma levels in ng/ml range, reduced inflammation and some protection but curcumin well tolerated at these high doses (Abdominal fullness, diarrhea) Reduced cytokines but increased brain derived-neurotropic factor; improved depression scores Faster recovery Reduced knee pain score Reduced pain and plasma cartilage specific marker Reduced arthritis score and plasma CRP; reduced use of painkillers Higher improvement in pain scores

4 One major problem Curcumin is very poorly absorbed even after 8 g/day, only ng levels can be detected in the plasma Therefore, the causal role of curcumin or definitive mechanism of action has not been established by animal studies Most studies demonstrating beneficial effects of curcumin are performed using cells and these effects are observed with much higher concentrations of curcumin than can be detected in the plasma Efforts are, therefore, directed towards making more curcumin available to the target cells We hypothesized that curcumin may be acting in the intestine and therefore, its absorption may not be necessary

5 Rationale for our hypothesis Intestine contains millions of bacteria that produce toxins (LPS) Neither the bacteria nor the toxin is released into the circulation Intestinal wall regulates this process and provides a barrier If this barrier was not present, the amount of bacterial toxins in the gut are enough to kill a human being!! If the intestinal barrier is breached and the intestinal bacteria or the bacterial products are released into the circulation slowly, it will cause inflammation and result in the development of diseases such as diabetes or heart or kidney disease

6 LPS (Active) Dephos. LPS (Inactive)

7 Curcumin protects the Intestinal Barrier No additions +LPS +LPS+Curcumin ZO-1 Claudin-1 Claudin-7 Actin 20 µm AJP (2017)

8 Clinical Trials with Curcumin Chow WD WD+C Work in progress

9 Clinical Trials with Curcumin Work in progress

10 WD Activity Disrupts WD MΦs Inflammation Permeability LPS MΦ infiltration into adipose tissue MΦ Activation MΦ infiltration into artery wall T2DM Atherosclerosis

11 Proposed model for the action of Curcumin PLoS One Sep 24;9(9):e Curcumin Heart Disease Diabetes Kidney disease

12 Thank you for your attention

14 Effect of Curcumin on Chronic Kidney Disease Control: Sham surgery NX: 5/6 th Nephrectomy Supplementation with Curcumin or Enalapril Collect Plasma Collect urine Evaluate Kidney Function

Enalapril Currently used drug for kidney disease

15 Supplementation with curcumin attenuates Kidney Disease Nx Animal model for kidney disease Enalapril Currently used drug for kidney disease Ghosh SS et el: Am J Physiol Renal Physiol. 296:F , 2009

weeks with or without oral curcumin Perform Glucose

16 Effect of Curcumin on Diabetes and Heart Disease LDLR-/- Mice Fed a High Fat High Cholesterol (Western Diet) for 16 weeks with or without oral curcumin Perform Glucose Tolerance test to evaluate diabetes Mice Sacrificed Evaluate Atherosclerosis

17 Supplementation with curcumin attenuates Western Diet-induced Diabetes and heart disease Ghosh SS et al. PLoS One. 9(9):e108577, 2014

18 LPS (EU/ml) Western Diet feeding promotes translocation of bacterial toxin (LPS) to circulation Chow * WD Specific Activity (% Chow Control) Chow * WD 2.5 * FITC (ng/µl) Chow WD

19 Supplementation with curcumin attenuates WD-induced increase in plasma LPS levels

20 Direction of movement of bacteria/bacterial products 4 IAP Anti- Bacterial Proteins LPS (Active) Dephos. LPS (Inactive) Systemic Circulation Lumen Outer Mucin Inner Mucin Cell Layer Goblet Cells Paneth Cells 1 2 3

Dietary supplementation in treating non-alcoholic fatty liver disease Dr. Ahmad Saedi Associate Professor School of Nutritional Sciences and

Dietary supplementation in treating non-alcoholic fatty liver disease Dr. Ahmad Saedi Associate Professor School of Nutritional Sciences and Dietetics Tehran University of Medical Sciences Honorary Academic