Zhaoping Li, MD, PhD Professor of Medicine Center for Human Nutrition

1

Zhaoping Li, MD, PhDProfessor of Medicine

Center for Human NutritionDavid Geffen School of Medicine, UCLA

Nutrition and Diabetes

糖尿病的营养疗法

Ascorbic Acid

Rich source for vitamins and minerals, low calorie, high fiber

Phytochemicals/Phytonutrients

Non-nutrient plant compounds

Provide health benefits against certain chronic human illnesses such as cancer, heart disease, neurodegenerative diseases, etc.

5Surh, Nature Reviews Cancer 3:768, 2003

Lycopen

• β-carotene, lycopene

• Ability to neutralize harmful byproducts of photooxidation

• Act as powerful antioxidants in humans– quenching singlet oxygen– scavenging free radicals

Bartley, G.E. and P.A. Scolnik. 1995. Plant carotenoids: pigments for photoprotection, visual attraction, and human health. The Plant Cell 7:1027–1038.Clinton, S.K. 1998. Lycopene: chemistry, biology, and implications for human health and disease. Nutrition Reviews 56(2):35–51.

Carotenoids

Pomegranate: Ellagitannin

Henning et al. 2009

OH

O

O

HO

OH

OHHO

HO

OH

OH

OO OO

CH2

O

O

OH

OHOH

OH

HO

O

O

HO

O

OO

MW = 1084

OH

OH

HO

Ellagic acid(MW = 302)

Pomegranate: Ellagitannin

Pentuk et al. 2006

•Antioxidant•Anti inflammation•Inhibit Angiogenesis•Anti-aromatase•Anti-proliferation

•Antioxidant•Anti inflammation•Inhibit Angiogenesis•Anti-aromatase•Anti-proliferation

Cruciferous Vegetables

• Sulforaphane (SFN), a prominent isothiocyanate

Increased nasal cell counts in response to DEP exposure are attenuated with BSE treatment

0.0

100.0

200.0

300.0

400.0

500.0

600.0

700.0

800.0

900.0

1000.0

0 6 24

Time Post-DEP (Hrs)

% o

f B

as

elin

e

Screen

Control

BSE

*

**

Sources of Resveratrol

• Resveratrol is found in– Grapes (only in skin)– Wine– Grape Juice– Peanuts– Blueberries– Bilberries– Cranberries

Benefits of Resveratrol• Induces apoptosis

(programmed cell death) in unhealthy cells

• Promotes normal nuclear factor kappa B and cyclooxygenase-2 activity

• Promotes normal activity of the SIRT-1 gene (involved in calorie restriction, fat mobilization, mitochondrial function, longevity)

• Promotes cardiovascular health – Normal platelet

activity– Normal

vasorelaxation– Antioxidant

protection of LDL particles

• Possibly Neuroprotective

14

Spices on Lipid Oxidation in Meat Patty

Li et al, ACJN April 2010

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Spices on Lipid Oxidation in Plasma

Li et al, ACJN April 2010

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Spices on Lipid Oxidation in Urine

Li et al, ACJN April 2010

Graph of normal endothelial function PAT signal tracings. The Endo–PAT2000 provides a very high degree of sensitivity and specificity as compared to the current Gold Standard of coronary artery endothelial function assessment – the coronary blood flow response to intra-coronary acetylcholine-infusion.

Assessing Endothelial Function

PAT

P=0.02

Urine MDA

P<0.001

Urine NOx

P=0.05

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Dihydrocapsiate on Energy Expenditure

Lee et al, Experimental Biology 2010

Avocado

PAT

A.

B.

*

Inflammatory Markers

A. IL-6

B. TNF-alpha

TURMERIC

Historical Uses:• Used as a condiment, healing remedy, and

textile dye• Used in Indian and Chinese medical systems

as an anti-inflammatory agent

AP-1

-catenin

CREB-BP

EGR-1

Notch-1

ERE

NF-B

HIF-1 WT-1

Nrf-2

PPAR-

STAT-1

STAT-3

STAT-4 STAT-5

Curcumin

Transcriptional factors

IL-1

IL-2

IL-5

IL-6

IL-8

IL-12

MCP

MIP

MaIP

TNF-α

IL-18

AATF-1

ATFase

ATPase

COX-2

5-LOX

Desaturase

DNA pol

FPT

GST

GCL

iNOS

MMP

NQO-1

ODC

PhP D

Src-2

Telomerase

TMMP-3

GlCL

AAPKCa2+PK

EGFR-K

ERK

FAK

IL-1R AK

JAK

JNK

MAPKPhK

PAK PKAPKB

Pp60c-tk

PTK

CTGF

EGF

FGF

HGF

NGFPDGF

TF

TGF-1

VEGF

AR

AHR

CXCR4

EGFR

EPCR

ER-αFas R

H2R

HER-2

IL-8 R

ITR

IR

LDLR

DR-5

ELAM-1

ICAM-1

VCAM-1

Bcl-2

Bcl-xL

IAP-1

Cyclin D1

Hsp-70

MDRP

uPA

DEF-40

p53

Inflammatory cytokines

Kinases

EnzymesGrowthfactors

Receptors

Others

Molecular targets upregulated

Molecular targetsdownregulated

Anand etal, CL, 2008

Piperine Enhance Curcumin Bioavailability

Planta Med. 1998 May;64(4):353-6.

Lipid Peroxide(nmoles/ml)

Total Cholesterol(mg/100ml)

7

6

5

4

3

2Pre Post Pre Post

250

220

190

160

130

100Pre Post

100

90

80

70

60

50

HDL-C(nmoles/ml)

Triglycerides(nmoles/ml)

300

260

220

180

140

100Pre Post

Changes in serum lipid levels in healthy subjects by curcumin

Ser

um

Lip

id l

evel

Sony & Kuttan, 1992

500 mg/day x 7days; N=10

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Pistachio

•Monounsaturated fatty acids

•Antioxidants

•Plant sterols

•Lutein

•Anthocyanins

•Resveratrol

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Calories and Fats not Equal

56 grams pistachios

=

53 grams pretzel

33

Pistachios Lower Triglycerides

* *

Base line 6 weeks 12 weeks

Pist

achi

os

Pret

zels

34

BMI

*

35

Tea

•NO Calories

•Tea Catechins

Green Tea Catechins

Green Tea Increases Metabolic Rate

•Increase metabolic rate

•Promotes fat oxidation

•Inhibit pancreatic lipase

•

Weight Loss by Green Tea

•Meta-analysis with 15 studies

•GTCs with caffeine reduce •BMI•Body weight•WC

Green Tea Effects on Diabetes

•1 - 2 cups/day

•Reduced incidence of Diabetes by 70%

•Decreased fasting glucose

Yonsei Med J. 2009 Feb 28;50(1):31-8. Epub 2009 Feb 24.

Cell. 2010 Sep 3;142(5):687-98

Macrophage Infiltration

: Decreased macrophages on HFD+ω3

HFD HFD+ω3

Supplements

Unknown: optimal therapeutic dosage, Unknown: optimal therapeutic dosage, effects of chronic use, potential toxicityeffects of chronic use, potential toxicity

Single compound works differently from Single compound works differently from whole foodwhole food

False sense of healthy life styleFalse sense of healthy life style