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Department of Internal Medicine, VCU Medical Center, Richmond, VA 23298-0050
Health Benefits of Turmeric/Curcumin
Shobha Ghosh, PhD, FAHAProfessor of Medicine and Physiology
Department of Internal Medicine
Department of Internal Medicine, VCU Medical Center, Richmond, VA 23298-0050
Department of Internal Medicine, VCU Medical Center, Richmond, VA 23298-0050
Clinical Trials with CurcuminTarget
Disease# Dose of Curcumin Findings
Obesity 2 1 g/day for 4 weeks500 mg/day for 12 weeks
Reduced IL-1β, IL-4, VGEFReduced LDL and lipid peroxidation
Metabolic syndrome
2 2 g/day for 12 weeks45-180 mg/day
Reduced LDL, TGNo effect
Diabetes 3 Meriva® (200mg/day) for 4 weeks200 mg/day for 9 months to pre-diabetics500 mg/day for 15-30 days
Improved blood flow in skin and retinaPrevention of diabetes developmentReduction 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 functionReduced liver fat, improved liver function
Cancer 13 6g/day with docetaxel for 6 cycles2g/day with radiotherapy
Dose escalation up to 8 g/day with docetaxel
Theracurmin (200 mg – 8 g) with Gemcitabine
Reduced PSA in this resistant populationReduces 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)
Depression 6 2 g/day along with anti-depressives
500 mg/day Curcumin with Fluoxetine
Reduced cytokines but increased brain derived-neurotropic factor; improved depression scoresFaster recovery
Arthritis 5 Theracurmin (150 mg/day) for 8 weeksFexofytol® (42 mg/day) for 3 monthsMeriva® (200 mg/day) for 3-8 months
Curcumin (500 mg/day) with diclofenac
Reduced knee pain scoreReduced pain and plasma cartilage specific markerReduced arthritis score and plasma CRP; reduced use of painkillersHigher improvement in pain scores
Department of Internal Medicine, VCU Medical Center, Richmond, VA 23298-0050
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
Department of Internal Medicine, VCU Medical Center, Richmond, VA 23298-0050
• 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
Rationale for our hypothesis
Department of Internal Medicine, VCU Medical Center, Richmond, VA 23298-0050
LPS (Active)
Dephos. LPS(Inactive)
Department of Internal Medicine, VCU Medical Center, Richmond, VA 23298-0050
Curcumin protects the Intestinal Barrier
No additions +LPS+Curcumin+LPS
Actin
Claudin-1
ZO-1
Claudin-7
20 µm AJP (2017)
Department of Internal Medicine, VCU Medical Center, Richmond, VA 23298-0050
Clinical Trials with Curcumin
Chow WD+CWD
Work in progress
Department of Internal Medicine, VCU Medical Center, Richmond, VA 23298-0050
Clinical Trials with Curcumin
Work in progress
WDWD
Activity
Disrupts
MΦsInflammationPermeability
LPS
MΦ Activation MΦ infiltration into artery wall
MΦ infiltration into adipose
tissue
T2DM Atherosclerosis
Department of Internal Medicine, VCU Medical Center, Richmond, VA 23298-0050
Department of Internal Medicine, VCU Medical Center, Richmond, VA 23298-0050PLoS One. 2014 Sep 24;9(9):e108577
Proposed model for the action of Curcumin
Curcumin
Heart DiseaseDiabetesKidney disease
Department of Internal Medicine, VCU Medical Center, Richmond, VA 23298-0050
Thank you for your attention
Department of Internal Medicine, VCU Medical Center, Richmond, VA 23298-0050
Effect of Curcumin on Chronic Kidney Disease
Control: Sham surgery
NX: 5/6th
Nephrectomy
Supplementation with Curcumin or
Enalapril
Department of Internal Medicine, VCU Medical Center, Richmond, VA 23298-0050
•Collect Plasma•Collect urine•Evaluate Kidney Function
Department of Internal Medicine, VCU Medical Center, Richmond, VA 23298-0050
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:F1146-57, 2009
Effect of Curcumin on Diabetes and Heart Disease
Perform Glucose Tolerance test to evaluate diabetes
Fed a High Fat High Cholesterol (Western Diet) for 16 weeks with or
without oral curcumin
Mice SacrificedEvaluate Atherosclerosis
Department of Internal Medicine, VCU Medical Center, Richmond, VA 23298-0050
LDLR-/- Mice
Department of Internal Medicine, VCU Medical Center, Richmond, VA 23298-0050
Supplementation with curcumin attenuates Western Diet-induced Diabetes and heart
disease
Ghosh SS et al. PLoS One. 9(9):e108577, 2014
Department of Internal Medicine, VCU Medical Center, Richmond, VA 23298-0050
LP
S (E
U/m
l)
Chow WD0
1
2
3
4*
Spec
ific
Activ
ity(%
Cho
w C
ontro
l)
Chow WD0
50
100
*
FITC
(ng/µ l
)
Chow WD0.0
0.5
1.0
1.5
2.0
2.5 *
Western Diet feeding promotes translocation of bacterial toxin (LPS) to circulation
Department of Internal Medicine, VCU Medical Center, Richmond, VA 23298-0050
Supplementation with curcumin attenuates WD-induced increase in plasma LPS levels
Department of Internal Medicine, VCU Medical Center, Richmond, VA 23298-0050
Systemic Circulation
Lumen
Outer MucinInnerMucinCell
Layer
1
4
3
2
Dire
ctio
n of
mov
emen
t of b
acte
ria/b
acte
rial
prod
ucts
IAP
Anti-Bacterial Proteins
PanethCells
Goblet Cells
LPS (Active)
Dephos. LPS(Inactive)