In adults with type 2 diabetes, does curcumin supplementation,

compared to a placebo or no supplementation, decrease

serum inflammatory markers?

Evidence Analysis Presentation

October 23, 2017
Brittnee Williams

Image: www.turmericcurcuminshop.com
 Background

• 1 out of every 11 people currently living with diabetes

• 1 out of every 4 veterans is living with diabetes
• 1 out of every 3 adults is living with prediabetes
• 2 out of every 5 people will develop type 2 diabetes in
their lifetime

Diabetes Latest. Centers for Disease Control and Prevention. https://www.cdc.gov/features/diabetesfactsheet/. Published June 17, 2014. Accessed September 29, 2017.
Close to 25 percent of VA Patients Have Diabetes. Veterans Health Administration Website. https://www.va.gov/health/NewsFeatures/20111115a.asp. November 15, 2011. Accessed September 29, 2017.
Inflammation and Diabetes

Insulin Disease
Diabetes
Resistance Progression

Inflammation
Turmeric (The Plant) Curuma longa

Image: Foremostco.com
Turmeric Rhizome (The Root)

Nelson K, Dahlin J, Bisson J, Graham J, Pauli G, Walters M. The Essential Medicinal Chemistry of Curcumin. J Med Chem. 2017;60(5):1620-1637
Molecular Targets
of Curcumin

Kunnumakkara A, Bordoloi D, Padmavathi G, Monisha J, Roy N, Prasad S, Aggarwal B. Curcumin, the golden nutraceutical: multitargeting for multiple chronic diseases. Br J Pharmacol. 2017;174(11):1325-1348.
Inflammation
and Diabetes

Meng B, Li J, Cao H. Antioxidant and Anti-inflammatory Activities of Curcumin on Diabetes Mellitus and its Complications. Curr Pharm Des. 2013;19(11):2101-2113.
Standards of Medical Care in Diabetes 2017

“There is no clear evidence that dietary

supplementation with vitamins, minerals, herbs, or
spices can improve outcomes in people with diabetes
who do not have underlying deficiencies.”
Question

In adults with type 2 diabetes, does curcumin supplementation,

compared to a placebo or no supplementation,
decrease serum inflammatory markers?
 Class A
Usharani 2008 (India)
Rating 

Study Design: Randomized, parallel-group placebo-controlled 8 week trial

Purpose: Curcuminoid supplementation, inflammatory markers/ET-1 in T2DM
Intervention Groups:
1. Two 150 mg capsules of NCB-02 twice daily (600mg/day)
2. One 10 mg Atorvastatin per day
3. Starch placebo twice daily

Outcomes: Significant reductions in MDA, TNF-α, IL-6 & ET-1 in NCB-02 Group
Conclusion: NCB-02 significantly reduced levels of inflammatory cytokines and markers
of oxidative stress with improved endothelial function
 Class A
Khajehdehi 2011 (Iran)
Rating 

Study Design: Randomized, double-blind, placebo-controlled 2 month trial

Purpose: Turmeric supplementation, biomarkers for renal function in T2DM nephropathy
Intervention Groups:
1. 500mg turmeric, 3 times daily (66.3mg/day)
2. Placebo 3 times daily

Outcomes: Significantly decreased serum and urinary IL-8

Conclusion: Turmeric may be a safe/effective alternative therapy for T2DM nephropathy.
 Class A
Na 2014 (China)
Rating 

Study Design: Randomized, double-blind and placebo-controlled, 3 month trial

Purpose: Curcuminoids, inflammation, adipocyte-fatty acid binding protein in T2DM
Intervention Groups:
1. 150mg of 97.49% curcuminoids twice daily (108mg/day)
2. Starch placebo twice daily

Outcomes: Significant decreases in fasting glucose, A1c, FFAs, serum A-FABP, CRP,
TNF-α, IL-6, and SOD; no significant effect on MDA

Conclusion: A-FABP links curcuminoids with effect on oxidative stress and inflammation
 Class D
Yang 2015 (China)
Rating -

Study Design: Non-controlled, 15-30 day trial

Purpose: Curcumin supplementation, diabetic kidney disease, antioxidative Nrf2 system
Intervention: 500 mg curcumin/turmeric daily (~500mg/day)
Outcomes: Significantly reduced MDA, LDL-C, U-mAlb, NQO-1, SOD1, SOD2 & IκB
Conclusion: Curcumin can prevent DKD through Nrf2 upregulation and attenuate DKD
by modulating gut microbiota, LPS, inflammatory pathway
 Results of Clinical Trials
MDA TNFα IL-6 LDL-C Glucose Curcumin
(nmol/mL) (pg/mL) (pg/mL) (mg/dL) (md/dL)
Pre Post P-value Pre Post P-value Pre Post P-value Pre Post P-value Pre Post P-value mg/day
Usharani No No
4.1 2.5 <0.001 4.1 2.1 <0.01 4.5 1.8 <0.01 120 111 155 150 600
2008 Data Data
Khajehdehi
12.8 18.4 0.82 IL-8 IL-8 0.002 114 110 0.71 179 156 0.21 66.3
2011
Na No No No
2.1 1.7 0.047 3.9 2.7 <0.001 77 68 0.115 154 131 <0.01 108
2014 Data Data Data
Yang No
13.9 3.5 <0.001 65 50 <0.01 148 146 ~500
2015 Data

Significant Decrease Non Significant Decrease Increase Not Measured

Study Limitations

Usharani Khajehdehi Na Yang

Quality Criteria Summary 2008 2011 2014 2015
VALIDITY QUESTIONS
2. Was the selection of study subjects/patients free from bias? Yes Yes Yes Unclear
2.1 Were inclusion/exclusion criteria specified (e.g., risk, point in disease
progression, diagnostic or prognosis criteria), and with sufficient detail and
without omitting criteria critical to the study? Yes Yes Yes No
2.2 Were criteria applied equally to all study groups? Yes Yes Yes N/A
2.3 Were health, demographics, and other characteristics of subjects
described? Yes Yes Yes Yes
2.4 Were the subjects/patients a representative sample of the relevant
population? Unclear Unclear Unclear Unclear
3. Were study groups comparable? No Yes Yes No
3.1 Was the method of assigning subjects/patients to groups described and
unbiased? (Method of randomization identified if RCT) No Yes Yes No
3.2 Were distribution of disease status, prognostic factors, and other factors
(e.g., demographics) similar across study groups at baseline? Unclear Yes Yes No
3.3 Were concurrent controls used? (Concurrent preferred over historical
controls.) Yes Yes Yes No
Study Limitations

Usharani Khajehdehi Na Yang

Quality Criteria Summary 2008 2011 2014 2015
6. Were intervention/therapeutic regimens/exposure factor or procedure
and any comparison(s) described in detail? Were intervening factors
described? Yes Yes Yes Unclear
6.1 In RCT or other intervention trial, were protocols described for all
regimens studied? Yes Yes Yes No
6.3 Was the intensity and duration of the intervention or exposure factor
sufficient to produce a meaningful effect? Yes Yes Yes Yes
6.4 Was the amount of exposure and, if relevant, subject/patient compliance
measured? No No Yes No
6.5 Were co-interventions (e.g., ancillary treatments, other therapies)
described? Yes Yes Yes No
6.6 Were extra or unplanned treatments described? No No No No
6.7 Was the information for 6.4, 6.5, and 6.6 assessed the same way for all
groups? Yes Yes Yes Yes
Study Limitations

Usharani Khajehdehi Na Yang

Quality Criteria Summary 2008 2011 2014 2015
8. Was the statistical analysis appropriate for the study design and type of
outcome indicators? No Yes Unclear No
8.1 Were statistical analyses adequately described the results reported
appropriately? Yes Yes No No
8.2 Were correct statistical tests used and assumptions of test not violated? Unclear Yes Unclear Unclear
8.3 Were statistics reported with levels of significance and/or confidence
intervals? Unclear Yes Yes No
8.4 Was “intent to treat” analysis of outcomes done (and as appropriate, was
there an analysis of outcomes for those maximally exposed or a dose-
response analysis)? No Yes No Unclear
8.5 Were adequate adjustments made for effects of confounding factors that
might have affected the outcomes (e.g., multivariate analyses)? No No Yes Unclear
8.6 Was clinical significance as well as statistical significance reported? Unclear Yes Yes Yes
8.7 If negative findings, was a power calculation reported to address type 2
error? No No No No
Conclusion Statement and Grade

Question: In adults with type 2 diabetes, does curcumin

supplementation, compared to a placebo or no supplementation,
decrease serum inflammatory markers?
Conclusion Statement Grade III:
Limited

There is no clear evidence that curcumin supplementation, compared to

a placebo or no supplementation, decreases serum inflammatory
markers in adults with type 2 diabetes. Combined, the studies show
curcumin interventions reduced MDA levels by 39-75%5,8, TNF-a by 19-
49%5-7, and IL-6 by 31-60%5,8 however, conflicting studies show no significant
effect on MDA7, and an increase in TNF-a8.
Implications for Patient Care at JAHAVA

• Not enough information

• Future research
• Mechanism of action
• Long term outcomes
• Molecular composition
• Clinical significance
• Recommend including a variety of herbs & spices in diet
 References
1. Diabetes Latest. Centers for Disease Control and Prevention. https://www.cdc.gov/features/diabetesfactsheet/. Published June 17,
2014. Accessed September 29, 2017.
2. Close to 25 percent of VA Patients Have Diabetes. Veterans Health Administration Website.
https://www.va.gov/health/NewsFeatures/20111115a.asp. November 15, 2011. Accessed September 29, 2017.
3. Nelson K, Dahlin J, Bisson J, Graham J, Pauli G, Walters M. The Essential Medicinal Chemistry of Curcumin. J Med Chem.
2017;60(5):1620-1637
4. Kunnumakkara A, Bordoloi D, Padmavathi G, Monisha J, Roy N, Prasad S, Aggarwal B. Curcumin, the golden nutraceutical:
multitargeting for multiple chronic diseases. Br J Pharmacol. 2017;174(11):1325-1348.
5. Usharani P, Mateen A, Naidu M, Raju Y, Chandra N. Effect of NCB-02, Atorvastatin and Placebo on Endothelial Function,
Oxidative Stress and Inflammatory Markers in Patients with Type 2 Diabetes Mellitus. Drugs R D. August 2008;9(4):243-250.
6. Khajehdehi P, Pakfetrat M, Javidnia K, Azad F, Malekmakan L, Nasab MH, Dehghanzadeh G. Oral supplementation of turmeric
attenuates proteinuria, transforming growth factor-β and interleukin-8 levels in patients with overt type 2 diabetic nephropathy: A
randomized, double-blind and placebo-controlled study. Scand J Urol Nephrol. 2011;45(5):365-370.
7. Na L, Yan B, Jiang S, Cui H, Li Y, Sun C. Curcuminoids Target Decreasing Serum Adipocyte-fatty Acid Binding Protein Levels in
Their Glucose-lowering Effect in Patients with Type 2 Diabetes. Biomed Environ Sci. 2014; 27(11):902-6.
8. Yang H, Xu W, Zhou Z, Liu J, Li X, Chen L, Weng J, Yu Z. Curcumin attenuates urinary excretion of albumin in type II diabetic
patients with enhancing nuclear factor erythroid-derived 2-like 2 (Nrf2) system and repressing inflammatory signaling efficacies. Exp
Clin Endocrinol Diabetes. 2015;123(6):360-7.