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Botanical Research Center
Pennington Biomedical
“Why an Apple a day
keeps the doctor away!”
“Why an Apple a day
keeps the doctor away!”
William T. Cefalu, M.D.
Pennington Biomedical Research Center
The “apple” Story!The “apple” Story!
Changing Nutrition/Health ParadigmChanging Nutrition/Health Paradigm
� What food is required for me?
� Nutritional deficiency:
� Iron - Anemia
� Iodine – Thyroid goiter
� Vitamin D - Rickets
� Identifying essential nutrients required for
promoting growth and sustaining life.
� Vitamins
� Essential minerals – Calcium
� Essential amino acids
1920s-1980s
Changing Nutrition/Health ParadigmChanging Nutrition/Health Paradigm
� What does food do to me?
� Nutritional excess and imbalances
� Calories - obesity
� Fiber – Colon cancer
� Identifying nutrients and components that
contribute to premature death
� Saturated fat
� Cholesterol
� Sodium
1950s-1990s
Seven Countries Study: CHD Events are
Correlated with Saturated Fat
Seven Countries Study: CHD Events are
Correlated with Saturated Fat
0 5 10 15 20
% Calories from Saturated Fat
0
1
2
3
4
5
CHD Deaths and MI/100 R = 0.84
V
MC
D
G
SW
B
Z
UN
E
K
Keys, 1970
Changing Nutrition/Health ParadigmChanging Nutrition/Health Paradigm
� What does food do for me?
� Nutritional optimization of quality of life
� Identification of physiological active
components to prevent or delay premature
onset of chronic disease
� Phytochemicals
� Pre/Probiotics
� Fiber
Functional Foods
1990s-Today!
Functional FoodsFunctional Foods
� Phytochemicals
� “Phyto” - Plant or “botanical” source
� Making a food “functional”
� Increase Phytochemicals
� Add Phytochemicals
� Replace phytochemicals
PolyphenolsPolyphenols
� Epicatechin
� Epigallocatechin
� Epigallocatechin gallate
� Source: Green tea; grapes, red wine
� Benefits: Anti-cancer; CHD protective
� Function: Inhibit chemical carcinogenesis and
tumor formation; inhibit cancer cell
growth; antioxidant; reduces free
radical/oxidative damage
CarotenoidsCarotenoids
� Lycopene
� β-carotene
� β-cryptoxanthin
� Lutein
� Source: Tomatoes, carrots, yams, cantaloupe,
spinach, sweet potatoes; citrus fruits
� Benefits: Anti-cancer; CHD protective
� Function: Antioxidant; free radical scavenger;
induction of cell-cell communication and
growth control; inhibit tumor growth
β-carotene
IsoflavonesIsoflavones
� Genistein
� Daidzein
� Source: Soybean, flaxseed
� Benefits: Relieves menopausal symptoms; prevents
osteoporosis; anti-cancer; CHD protective
� Function: Estrogen-like activity; inhibit growth of
breast cancer cells; stimulate Ca
absorption; lower cholesterol levels
Genistein
FlavonoidsFlavonoids
� Quercetin
� Apigenin
� Luteolin
� Myricetin
� Source: Citrus fruits; vegetables
� Benefits: Heart protection; Increase stamina
� Function: Antioxidant; inhibit platelet aggregation;
inhibit cancer cell growth and
proliferation; cytotoxic to cancer cells
Luteolin
The Promise of Functional FoodsThe Promise of Functional Foods
� Better health through improved nutrition
can:
� Increase quality of life
�Enhance productivity
�Reduce health-care costs
- by preventing or delaying the onset of
chronic disease, i.e diabetes
- or improving metabolic factors related to the
disease, i.e. glucose
Health claims need to
be verified
with carefully controlled studies
Botanical (Natural) Supplements
29,000 supplements available to American consumer
Diabetes: the growing global burden
IDF:2 %• Diabetes currently affects 246 million people worldwide• It is expected to affect 380 million by 2025
No data
< 2%
2–5%
5–8%
8–11%
11–14%
14–17%
> 17%
20002000Prevalence estimates of diabetes mellitusnts'Ffsmys2se:bu F:se2i %2abF(s:se2u sffb:ce 3&&"3&&"
No data
< 2%
2–5%
5–8%
8–11%
11–14%
14–17%
> 17%
Prevalence estimates of diabetes mellitus 2003200320032003
No data
< 2%
2–5%
5–8%
8–11%
11–14%
14–17%
> 17%
Prevalence estimates of diabetes mellitus 2025202520252025
No data
< 2%
2–5%
5–8%
8–11%
11–14%
14–17%
> 17%
BrainCerebrovascular disease
• Transient ischemic attack
• Cerebrovascular accident
• Cognitive impairment
Complications of Diabetes
HeartCoronary artery disease
• Coronary syndrome• Myocardial infarction• Congestive heart
failure
ExtremitiesPeripheral vascular disease• Ulceration• Gangrene• Amputation
Large Blood Vessel Small Blood Vessel
NervesNeuropathy
• Peripheral• Autonomic
KidneyNephropathy
• Microalbuminuria• Gross albuminuria• Kidney failure
EyeRetinopathyCataractsGlaucoma
Prevalence of Diagnosed Diabetes in Adults2003
Prevalence of Diagnosed Diabetes in Adults2003
Insulin receptor
“SWITCH”
Plasma
membrane
Glucose carriers move
to the surface
Blood
Sugar
Insulin
Chemical Signals
Insulin Action (“Sensitivity”) in Muscle and Fat Insulin Action (“Sensitivity”) in Muscle and Fat
Carriers insert into
cell surface
Blood Sugar enters body
Glucose
(“sugar”)
carriers
GLUT4=glucose transporter 4
Insulin “Efficiency”
“Pre-Diabetes” (Insulin “inefficiency)
“Pre-Diabetes”
Type 2 diabetes
Years from
diagnosis0 5-10 -5 10 15
Pre-diabetes
Onset Diagnosis
Insulin secretion
Insulin “inefficiency
Ramlo-Halsted BA, Edelman SV. Prim Care. 1999;26:771-789 Nathan DM. N Engl J Med. 2002;347:1342-1349
Post-Meal glucose
Fasting glucose
Pancreas function
Progressive β-Cell Failure
Natural History of Type 2 Diabetes
PLASMA GLUCOSE
Normal: 99 mg/dl or less
Pre-Diabetes: 100-125 mg/dl)
Diabetes > 126 mg/dl fasting);
> 200 mg/dl )(PostPrandial)
Re
lati
ve
Ris
k o
f M
I o
r S
tro
ke
0
1
2
3
4
5
6
7
Nondiabetic
Throughout
2.4
>15 Yr
Before Dx
10-14.9 Yr
Before Dx
3.64
<10 Yr
Before Dx
Diabetic
Throughout
5.02
3.19
1.0
Hu FB, et al. Diabetes Care. 2002;25:1129-1134.
Non-Diabetic Diabetes
Cardiovascular Risk in Pre-diabetes
Pre-Diabetes
Obesity
Insulin inefficiency (“resistance”)
Abnormal
Lipids
Elevated
Blood Pressure
Blood Vessel
Dysfunction
Heart Disease
Physical
Inactivity Aging
High Blood Sugar
“Metabolic” Syndrome
Modified from S. Grundy MD
High Waist/Hip
(≥0.95 in men)
(≥0.80 in women)
Low Waist/Hip
(<0.95 in men)
(<0.80 in women)
An Index of Abdominal vs Peripheral Obesity
Body Shape Matters!!!
“Central” obesity
Body Shape Matters!!!
“Central” obesity
Visceral Fat Distribution:
Normal vs Type 2 Diabetes
Visceral Fat Distribution:
Normal vs Type 2 Diabetes
Type 2 DiabetesNormal
Larsson. Acta Med Scand Suppl. 1988;723:45-51.
Risk of diabetes mellitus during 13 years in relation to WHR at baseline.
Comparison between these in upper and lower 10% of WHR distribution.
Waist Measurement and
Diabetes Risk
Waist Measurement and
Diabetes Risk
25
20
15
10
5
054
Age
Ris
k (
%)
Upper 10% Waist to hip ratio
Lower 10% Waist to hip ratio
55 56 57 58 59 60 61 62 63 64 65 66 67
Cumulative hazard (%)
Follow-up (y)
YES
Metabolic Syndrome
NO
Heart Disease Deaths
0 2 6 8 124 100
5
10
15
Death Increases with Metabolic Syndrome
“Pre-Diabetes”
Type 2 diabetes
Years from
diagnosis
0 5-10 -5 10 15
Pre-diabetes
Onset Diagnosis
Insulin
“Inefficiency”
Ramlo-Halsted BA, Edelman SV. Prim Care. 1999;26:771-789 Nathan DM. N Engl J Med. 2002;347:1342-1349
Post-Meal glucose
Fasting glucose
Natural History of Type 2 Diabetes
Nutrition and Exercise
Reduces progression to diabetes by 60%
Type 2 diabetes
Years from
diagnosis0 5-10 -5 10 15
Pre-diabetes
Onset Diagnosis
Insulin
“Inefficiency”
Ramlo-Halsted BA, Edelman SV. Prim Care. 1999;26:771-789 Nathan DM. N Engl J Med. 2002;347:1342-1349
Post-Meal glucose
Fasting glucose
Natural History of Type 2 Diabetes
“Nutraceutical /Phytochemical)
Strategies”
Increased Consumption of
“Functional Foods”
Nutrition and Exercise
Reduces progression to diabetes by 60%
Blueberries Improved
the Ability of Insulin to Work
Blueberries Improved
the Ability of Insulin to Work
22.2
4.9
0
5
10
15
20
25
Blueberry Placebo
%∆
In
suli
n S
ensi
tivit
y
∆ insulin Sensitivity = ability of insulin to work from week 0 to week 6
4-Fold
Louisiana Agriculture and Diabetes
Sugar Cane can fight Diabetes?
Wang ZQ, Zuberi AR, Zhang XH, Macgowan J, Qin J, Ye X, Son L, Wu Q, Lian K, Cefalu WT. Effects of dietary fibers on
weight gain, carbohydrate metabolism, and gastric ghrelin gene expression in mice fed a high-fat diet. Metabolism. 2007
Dec;56(12):1635-42.
Tarragon and DiabetesTarragon and Diabetes
� Extract of Artemisia
dracunculus with
antidiabetic properties
� Produced from
hydroponically grown
plants under controlled
conditions
Russian tarragon
Potential Lifetime Impact for Pre-Diabetes
Intervention
83%75%63%
% Developing Diabetes over Lifetime
Diabetes Onset
$1755$ 635
Aroda VR, Ratner R. JCEM 93(9):3259-65, 2008
Life Expectancy: Increase by
0.5 Years
Macrovascular Microvascular
Potential Lifetime Impact for Pre-Diabetes
Lifestyle Intervention
Aroda VR, Ratner R. JCEM 93(9):3259-65, 2008
Stroke
9%
Coronary Heart Disease
8%
Amputations
35%
Blindness
39%
End Stage Renal Disease
38%
Summing it all upSumming it all up
“Eat and Drink the Rainbow”