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Cures in the Cupboard: Foods that Fight Disease
Sources of Vitamin A
Carrots SweetpotatoesPumpkin Tomatoes
Red Sweet Pepper SpinachCollards Turnip Greens
Kale BeetGreen Leaf Lettuce Romaine Lettuce
Cantaloupe MangoRed & Pink Grapefruit Apricots
Sources of Vitamin C
Citrus Fruits Kiwi FruitStrawberries Guava
Papaya CantaloupeBroccoli PeppersTomatoes Spinach
Brussels Sprouts PotatoesLeafy Greens Turnip Greens
Cabbage
Sources of Potassium
Baked White or Sweetpotatoes Cooked GreensWinter (orange) Squash Bananas
Plantains Dried FruitsOranges & Orange Juice Cantaloupe
Tomatoes SpinachHoneydew Melons Cooked Dry Beans
Soybeans Tomato ProductsBeet Greens
Avg. Fruit & Vegetable ConsumptionNationwide, 1996 vs. 2002
5+ times a day3 or 4 times a day
1 or 2 times a dayNever or <1 a day
50
40
30
20
10
0
Percent (Median)
19962002
Garlic: Health Benefits• Antibiotic/antifungal effects
• Antiseptic properties useful in fighting infections and dysentery-causing amoebas
• Antioxidant effects, protecting cells from free-radical damage and cancer
• Cholesterol reduction, lowering LDL and increasing HDL
• Natural anticoagulant properties, preventing blood clots and strokes
• Anti-hypertensive effects, reducing blood pressure.
Powerful Antioxidants
Orange JuiceGreen Tea
Cranberry Juice CocktailBlueberry Juice
Red WinePomegranate Juice
7
6
5
4
3
2
1
0
Polyphenols (mM)
Free Radicals Neutralized
Green TeaOrange Juice
Cranberry Juice CocktailBlueberry Juice
Red WinePomegranate Juice
80
60
40
20
0
Percent
Fruit Nutritional Information
Relative to White, non-Hispanic households,Asian and Hispanic ones purchase more variety, Black
households buy fewer types of vegetables, but spread out their purchases more evenly across what they do buy
Demographics Are Key to Variety
Race & Ethnicity Are ImportantAs measured by the Simpson index, Asian and Hispanic
households spread out their vegetable purchases 23 percent and 6.5 percent more evenly than White, non-Hispanic
households do.
Best Sources Of Food AntioxidantsAs Measured By Total Antioxidant Capacity Per Serving Size
Rank Food Item Serving Size
1 Small Red Bean (Dried) Half cup
2 Wild Blueberry 1 cup
3 Red Kidney Bean (Dried) Half cup
4 Pinto Bean Half cup
5 Blueberry (Cultivated)
1 cup
6 Cranberry 1 cup (whole)
7 Artichoke (Cooked) 1 cup (hearts)
8 Blackberry 1 cup9 Prune Half cup
10 Raspberry 1 cup
Fruit & Vegetable ConsumptionPer Capita Percent Change, 2000 to 2020
Citrus Apples Grapes Other Fruit
-8.6%
Fried Potatoes & Chips
Other Potatoes
Tomatoes Lettuce Other Vegetables
7.4% 7.8%
5.1%
7.0%
1.3%
5.1%3.6%
-3.0%
Effects of Rising IncomeOn Per Capita Fruit & Vegetable Consumption
Commodities
Total Income Effect
Direct Income Effect Eating Out Knowledge
Fruit Citrus 1.87 1.85 -1.77 1.83 Apples 1.93 1.95 -1.81 1.81 Grapes 1.23 1.21 -1.42 1.48 Other Fruit 1.48 1.36 -1.22 1.36
Vegetables Fried Potatoes and Chips 0.19 -0.47 1.75 -1.08 Other Potatoes -1.86 -2.53 0.49 0.19 Tomatoes 0.86 0.76 -0.01 0.11 Lettuce 2.12 1.42 0.18 0.5 Other Vegetables 0.65 0.63 -0.46 0.47
Indirect Income Effects
Percent
Carotenoids
Alpha-Carotene Carrots Neutralize Free Radicals
Beta-Carotene Fruits, Vegetables
Neutralize Free Radicals
LuteinGreen
Vegetables
Reduced Risk Of Macular
Degeneration
LycopeneTomato Products
(Ketchup, Sauces)
Reduced Risk Of Prostate Cancer
Examples of Functional Components
Fatty Acids
Omega-3 Fatty Acids-DHA/EPA
Tuna And Other Fish Oils
Reduced Risk Of Cardiovascular
Disease And Improved Mental, Visual Functions
Conjugated Linoleic Acid CLA
Cheese, Meat Products
May Improve Body Composition, May Decrease Risk Of Certain Cancers
Examples of Functional Components
Flavonoids
Anthocyanidins Fruits
Catechins Tea
Examples of Functional Components
Neutralize Free Radicals, May Reduce
Risk Of Cancer
Prebiotics/Probiotics
Fructo-Oligosaccharides
(FOS)
Jerusalem Artichokes,
Shallots, Onion Powder,
Lactobacilius Yogurt, Other Dairy
Examples of Functional Components
May Improve Quality Of Intestinal Microflora
The Power of Diet & Lifestyle Changes
Dean Ornish, M.D.President, Preventive Medicine Research Institute
Clinical Professor of Medicine, UCSFMilken Institute Global Conference
April 18, 2005
Your body has a remarkable capacity to begin healing itself if you give it a chance to do so.
Optimal Lifestyle Program
• Diet (low-fat, whole foods, plant based)• Stress management training • Moderate exercise• Smoking cessation• Psychosocial support groups• Supplements
High fat, Low-fat, Meat-based Plant-based
• High in cholesterol• High in saturated fats• High in oxidants• Low in antioxidants• Inflammatory• Low in fiber
• No cholesterol• Low in saturated fats• Low in oxidants• High in antioxidants• Prevents
inflammation• High in fiber
Omega-3 Fatty Acids (“Good Fats”)
• May reduce sudden cardiac death by 50-80% or more
• May reduce risk of prostate cancer, breast cancer, and colon cancer
• Only 3 grams/day provide protective benefits
An Optimal Diet is—• Low in refined (“bad”) carbohydrates• High in unrefined (“good”) carbohydrates• Low in meat-based proteins• High in plant-based proteins• Low in saturated fats and trans fats• 3 grams/day of omega-3 fatty acids
To the degree you move in this direction on the food spectrum, you lose weight, feel better, and gain health.
Can Lifestyle Changes Reverse Coronary
Heart Disease?
201 Thallium Myocardial ScintigraphyCase D
May 15, 1978 June 15, 1978
Changes in Quantitative Coronary Arteriography
5 y (P=.001)1 y ( P=.02)Baseline (n.s.)
52
50
48
46
44
42
40
38
36
Percent Diameter Stenosis
ControlTreatment
Conclusions: More regression of coronary atherosclerosis occurred after 5 years than after 1 year in the experimental group. In contrast, in the control group, coronary atherosclerosis continued to progress and more than twice as many cardiac events occurred.
JAMA. 1998;280:2001-2007
Adherence and Change in Coronary Atherosclerosis After 5 years
High (>88%)Intermediate (56-88%)Low (<56%)
2
0
-2
-4
-6
-8
Percent
Control
1% Experimental
55% 45%
99%
100 80 60 40 20 20 40 60Better or No Change, % Worse, %
P=.03
There was a 40% reduction in LDL-cholesterol in the Lifestyle Heart Trial after one year without drugs.
Ornish D et al. JAMA. 1998;280:2001-2007.
$20 billion were spent last year on statin drugs, most of which could be avoided by
making comprehensive lifestyle changes instead.
The Multicenter Lifestyle
Demonstration Projects
Medical EffectivenessDemonstration Projects
• Three demonstration projects• More than 2,000 patients• Greater changes in diet and lifestyle,
larger improvements in risk factors and quality of life, and bigger cost reductions than have ever before been reported in an ambulatory group of patients.
Implementation of Demonstration Projects
A physician supervises and directs the behavioral intervention, assisted by a team of health professionals:– Nurse case manager– Registered dietitian– Clinical psychologist (support groups)– Exercise physiologist– Stress management instructor– Program director
1. The Multicenter Lifestyle Demonstration Project
•Almost 80% of 333 patients who were eligible for bypass surgery or angioplasty were able to safely avoid it for at least three years with comparable safety & benefits compared to a matched control group.•Ornish D. Avoiding revascularization with lifestyle changes: The Multicenter Lifestyle Demonstration Project. American Journal of Cardiology. 1998;82:72T-76T. •Koertge J, Weidner G, Elliott-Eller M, et al. Improvement in medical risk factors and quality of life in women and men with coronary artery disease in the Multicenter Lifestyle Demonstration Project. American Journal of Cardiology. 2003;91:1316-1322.
1. The Multicenter Lifestyle Demonstration Project
• Mutual of Omaha calculated saving an average of $29,529 per patient.
•Ornish D. Avoiding revascularization with lifestyle changes: The Multicenter Lifestyle Demonstration Project. American Journal of Cardiology. 1998;82:72T-76T. •Koertge J, Weidner G, Elliott-Eller M, et al. Improvement in medical risk factors and quality of life in women and men with coronary artery disease in the Multicenter Lifestyle Demonstration Project. American Journal of Cardiology. 2003;91:1316-1322.
2. The Highmark Blue Cross Blue Shield Demonstration Project: Cost Comparisons After 3 Years
Experimental Group (CAD) vs. Matched Cohort (CAD) Members Year by Year
Experimental Group (CAD) (N=75) Baseline vs. 3 year average = 8.7% decrease in costs
Matched Cohort Members (CAD) (N=75) Baseline vs. 3 year average = 47.2% increase in costs
Year 3Year 2Year 1Baseline
9000
8000
7000
6000
5000
4000
US$
Ornish Members CADMatched Cohort Members
3. The Medicare Lifestyle Demonstration Project (MLMPD)
•The risks of bypass surgery & angioplasty increase with age but the benefits of comprehensive lifestyle changes are as great in older patients as in younger ones
•Therefore, comprehensive lifestyle changes are especially beneficial in Medicare patients
WeightAll Participants (N = 2,108)
1 Year12 WeeksBaseline
200
195
190
185
180
175
LBS
Body Mass IndexAll Participants (N = 2,108)
1 Year12 WeeksBaseline
32
31
30
29
28
27
BMI
AnginaAll Participants (N = 2,108)
1 Year12 WeeksBaseline
30
25
20
15
10
5
% of Participants with Any Angina in Preceding 30 Days
Functional Capacity (METs)All Participants (N = 2,108)
1 Year12 WeeksBaseline
11.0
10.5
10.0
9.5
9.0
8.5
8.0
7.5
METs
SF-36 General Health/Quality of LifeAll Participants (N = 1,908)
1 Year12 WeeksBaseline
75
70
65
60
55
1 Year12 WeeksBaseline
150
145
140
135
130
125
mm HG
Hypertensives – Systolic BP
N at 1 year is not comparable to baseline because many patients have not yet finished 1 year of intervention
All p<.001
1 Year12 WeeksBaseline
86
84
82
80
78
76
74
mm HG
Hypertensives – Diastolic BP
N at 1 year is not comparable to baseline because many patients have not yet finished 1 year of intervention
All p<.001
Diabetics - HbA1c
All p<.001Data to be presented at APS, 2005
Data for patients who have reached 1 year of testing
1 Year12 WeeksBaseline
7.6
7.4
7.2
7.0
6.8
6.6
6.4
Percent
Summary of These Three Demonstration Projects:
• “Medicare coverage of this program would reduce Medicare expenditures even under a set of more pessimistic assumptions then I felt were appropriate.”
--Roland E. (“Guy”) King Chief Actuary, Medicare, 1978-1994
Can Lifestyle Changes Reverse the Progression of
Prostate Cancer?
• Principal Investigator: • Dean Ornish, M.D.Clinical Professor of Medicine, UCSF• Co-Principal Investigators:• Peter Carroll, M.D.Chairman & Professor, Dept. of Urology, UCSF • William Fair, M.D.Chairman & Professor, Dept. of Urologic SurgeryMemorial Sloan-Kettering Cancer Center
Patient Selection Criteria
• 90 men with biopsy-proven prostate cancer, PSA 4-10, Gleason <7
• All patients chose to do watchful waiting for reasons unrelated to this study
• Randomly assigned to comprehensive lifestyle changes or usual care
None of the experimental group patients but six
control group patients had conventional treatment
during the first year.
Changes in PSA
P = 0.002
12 MonthsBaseline
6.80
6.60
6.40
6.20
6.00
5.80
Control (n=41)Experimental (n=43)
Degree of Lifestyle Change and Changes in PSA
P= 0.001
High (>88%)Medium (48-88%)Low (<48%)
8
6
4
2
0
-2
-4
-6
Percent
Change in Prostate Tumor Growth
t = -6.9, P = .000
-9%
-70%
-70%
-55%
-40%
-25%
-10%
%FBS
ControlExperimental
Degree of Lifestyle Change and Inhibition of LNCaP Tumor Growth
0
-20
-40
-60
-80Baseline-12m change in LNCAP cell growth
Dietary Adherence and Changes in C-Reactive Protein
High (>97%)Medium (81-97%)Low (<81%)
0.00
-0.10
-0.20
-0.30
-0.40
Baseline-12m change in (log)CRP
1 year laterPSA - 4.5 ng/ml
BaselinePSA - 6.4 ng/ml
Can Pomegranate Juice Affect the Progression
of Coronary Heart Disease?
Blow Flow to the Heart
+1.18
-0.70
-0.80
0.20
1.20
%FBS
ExperimentalControl
P < 0.05
Threat of Litigation & Legislation
Diet and Diabesity
Francine Ratner Kaufman, M.D.Professor of Pediatrics
The Keck School of Medicine of USCHead, Center for Diabetes and Endocrinology
Childrens Hospital Los Angeles
Geneticsusceptibility Environmentalfactors
AtherosclerosisHyperglycemiaHypertension
RetinopathyNephropathyNeuropathy
BlindnessRenal failureCHDAmputation
Onset ofdiabetes
Complications
Disability
DeathOngoing hyperglycemiaPRE
Obesity Insulin resistance
Risk forDisease
MetabolicSyndrome
Natural History of Diabesity
Male Teens12-17
Female Teens12-17
Percentage of Overweight Children Youth3-4 Fold Increase in 30 Years
Perc
enta
ge
Boys 6-11 Girls 6-110
2
4
6
8
10
12
14
16
1963–70 1971–74 1976–80 1988–94 1999–2000
Health and Healthy Weight
Diabetes Trends Among Adults in the USBRFSS 1990, 1995 and 2001
Burden of Diabetes in USA
• 18.2 Million Americans Have Diabetes • 5.2 Million Unaware of Diagnosis• 40 Million Americans Have Prediabetes• 239,000 Diabetes-Related Deaths/Year• 2-to-6-Fold More Likely to CVD• 75% of Diabetes Deaths Associated With
CVD • Cost $132 Billion/2002
The U.S. Diabetes Prevention ProgramIntensive Lifestyle Intervention: Goals
• > 7% loss of body weight and maintenance of weight loss– Dietary fat goal -- <25% of calories from fat– Calorie intake goal -- 1200-1800 kcal/day
• > 150 minutes per week of physical activity
0 1 2 3 40
10
20
30
40PlaceboPlaceboLifestyleLifestyle
Years on TrialYears on Trial
Cum
ulat
ive
Inci
denc
e (%
)C
umul
ativ
e In
cide
nce
(%)
U.S. Diabetes Prevention ProgramEffect of Intensive Lifestyle on Diabetes Rates
58% Relative Risk Reduction
Finnish Diabetes Prevention StudyEffect of Intensive Lifestyle on Diabetes Rates
0.5
0.6
0.7
0.8
0.9
0 1 2 3 4 5 6
Years on Trial
Intensive LifestyleControl
Frac
tion
With
out D
iabe
tes
58% Relative Risk
Reduction
US National Weight Control Registry
• Lost and maintained minimum weight loss of 13.5 kg for 5 years
• 1380 calories 24% from fat = standard carbohydrate and low fat diet
• Very active expend - 400 kcal/d in PA• Physical activity predicted weight
maintenance
IOM, ADA and ADietA Nutrition Recommendations
• Carbohydrate – 45-65%
• Fat – 20-35%
• Protein – 0.8 g/kg body weight/d– 10-35%
Carbohydrate Recommendations from ADA for Diabetes
• Amount (grams) of carbohydrate and type of carbohydrate influence blood glucose levels
• Monitoring total grams of carbohydrate a key strategy
• Use of glycemic index/glycemic load provides additional benefit – 37% increased risk of type 2 diabetes for women
with highest dietary glycemic index• Low carbohydrate diets (restricting total
carbohydrate to <130 g/day) not recommended
Low Carbohydrate• Low carbohydrate diets may enable short term weight
loss• Poor dietary compliance over long term• Foster, et al NEJM, 2003:
– < 10% carbohydrate, 50-60 fat, 30-35 protein– Greater weight loss at 6 months - very low carb diet
vs low fat – No difference at 1 year between groups
• Bravata, et al JAMA, 2003:– Meta analysis of low carbohydrate diet <60 g – Weight loss associated with reduced calories and
longer duration of diet rather than carbohydrate intake
– Of 2681 who lost >13 kg for 1 year, less than 1% maintained weight loss
• CARDIA Study – Fasting Insulin and 2-Hour glucose levels inversely
related to amount of fiber • Reduces Risk of Diabetes
– RR for >8.1 g/day versus <3.2 g/d was 0.70, 95% CI: 0.51–0.96, p 0.007
• Improves Hyperinsulinism– High fiber diet reduced insulin responses in
hyperinsulinemic men– Dark yellow and green leafy vegetables reduce risk
FIBER
Red Meat and Processed MeatWomen’s Health Study
• 37,309 participants over 8.8 years > 45 years of age• During 326,876 person-years of follow-up , 1558
cases of diabetes documented.• Adjusted for age, BMI total energy intake,
exercise, alcohol, cigarettes, FH of type 2• Positive association between red meat and
processed red meat and type 2 • Similar to Health Professionals Follow-up Study
for men
Fruits and Vegetables• 577 adults, diet high in fruits and
vegetables reduce 6-year incidence of type 2 by 24%– Da Qing IGT and Diabetes Study Total
fruit and vegetable intake
• Women’s Health Study – 39,876 subjects – 2.2 + 1.6 fruits; 3.9 + 2.6 vegetables– Dark yellow and green leafy vegetables – RR .8 even for overweight women
Fat and Diet• Irrefutable -high fat diets cause insulin resistance• Low fat diets safe, weight and improve CVD
– Diets with 20-30% of energy from fat• Dutch and Finnish Cohorts - Seven Countries Study
– 30-year follow-up - role of dietary fat intake in glucose intolerance and diabetes incidence
• San Luis Valley Diabetes Study – Increase in fat intake of 40 grams per day associated with 3.4-
fold increase in type 2 diabetes risk • Health Professionals Follow-up Study
– Positive relationships between total and saturated fat and risk of type 2 diabetes
Overweight Children Compared to Normal Weight
• Ate fewer fruits and vegetables (2.9 vs. 3.3/day)• Drank more sweetened beverages (1.3 vs.
1.1/day)• Ate more high-fat snacks (64 vs. 56 %)• Ate more fast food (1.4 vs. 1.1/week)• Less likely take part in lessons on nutrition • (50 vs. 64 %)
Teenage boys 2.2 sodas/day = 800 cans/year• Teenage girls 1.7 sodas/day• Teens consume 2X amount of sugar than
recommended = 44% from soft drinks• Evidence – 1 extra soda increases risk for
overweight by 60%
Sweetened Beverage Consumption
School-based Program to Decrease Soda Consumption
• 644 children (7-11 years old), 6 schools• Program to decrease regular and diet soda
intake delivered in 1-hour sessions 4 times per year
!!!! 7.5!!!! 0.2 Control"""" 0.2"""" 0.6Intervention
% Overweight and Obese
# Glasses of Soda Per Day
Nutrition Practices to Combat Diabesity –ADA Recommendations
• Decrease total calories • Decrease dietary fat• Decrease energy density of foods • Increase fruits and vegetables • Decrease sweetened beverages including juice• Decrease fast food consumption • Avoid skipping meals, particularly breakfast• Decrease snacking on unhealthy foods
Effects of Food Preferences and Aversions on Healthy Eating
• Alexandra W. Logue, Ph.D.Vice President for Academic Affairs and ProvostNew York Institute of Technology
Food Preferences and Aversions
• Salty food
• Sweet food
• High-density calorie food
• Bitter food
Number of People for Whom a Given Concentration of PTC is the Lowest Concentration Tasted
Bruce N. AmesChildren’s Hospital Oakland Research InstituteProfessor, University of California, Berkeley
A Major Role For MicronutrientsIn Disease Prevention
18 April 2005Milken, LA
O2 O2-
e- e- e- e-H2O2 •OH H2O
~30% Smoking~35% Unbalanced Diets
Too Many Calories: ObesityToo Little Fiber & Micronutrients
~20% Chronic InfectionsMostly in Poor Countries
~20% HormonesBreast, Endometrial, Etc.
~2% Occupation<1% Pollution
Mostly Heavy Air Pollution
The Causes of Cancer
Total = 107% because of multiple causes
Micronutrient Undernutrition in Americans
• Wakimoto and Block (2001) J Gerontol A Biol Sci Med Sci. Oct; 56 Spec No 2(2):65-80.** Before U.S. Food Fortification
25%50%90; 75 mgMen; WomenC
5; ~10-25%10-20; 25-50 %2.4 mcgMen; WomenB12
25%; 50%75%400 mcgMen; WomenFolate**
10%50%1.7; 1.5 mgMen; WomenB6 Vitamins
5-10%25%8 mgWomen 50+ years
25% 75%18 mgWomen 20-30 years Iron Minerals
<50% RDA% ingesting< RDAPopulation GroupNutrient RDA
% ingesting
Zinc Men; Women 50+ years 11; 8 mg 50% 10%
dUMP dTMP
Methionine
SHMT
B6
Serine
MTHFR
Homocysteine
(polymorphism)
TS
MS
CH2=THF
B12CH3-THF
Micronuclei in: RNA positive erythrocytesRNA negative erythrocytes
Folic AcidFolinic Acid
TIME (DAYS)
1 yearpreRx
Normalrange
Mic
ronu
clei
per
100
0 ce
lls
20
50 100 150 200 250 300 350
0
30
40
80
130
xx
PLASMA FOLATE (NG/ML)
MIN
PC
Es/
1000
PC
Es
60
50
40
30
20
10
00 5 10 15 20 25 30
0
0.5
1
1.5
2
2.5
3
3.5
0 2 4 6 8 10 12
Avg
50 c
omet
sHuman Lymphocyte DNA Strand Breaks
(Comet Assay) vs. B-6 Intake
Vitamin B-6 Intake
Folate, Vitamin B12, Homocysteine Status and Chromosome Damage Rate in Lymphocytes of Older MenMichael Fenech, Ivor Dreostl, and Josephine Rinaldi, Carcinogenesis 13:1329-1336, 1997
Folate, Vitamin B12, Homocysteine Status and DNA Damage in Young Australian AdultsMichael Fenech, Claire Aitken, and Josephine Rinaldi, Carcinogenesis 19:1163 - 1173, 1998
Micronucleus Frequency in Human Lymphocytes is Related to Plasma Vitamin B12 and Homocysteine
Michael Fenech, Mutation Research 42: 299 - 304, 1999
In a series of studies, we have been able to confirm that the micronucleus index in cytokinesis-blocked lymphocytes is significantly negatively correlated with plasma vitamin B12 (B12) concentration and significantly positively correlated with plasma homocysteine (HC). Furthermore we have shown in a randomized double-blind placebo-controlled dietary intervention study that intake of 3.5 times the RDI of folic acid and B12 significantly reduces the micronucleus index only in those with above average levels of micronucleus frequency. Micronucleus frequency is minimized when plasma HC is below 7.5 µmol/l and plasma B12 is above 300 pmol/l. Therefore, it is important to take account of the effect of B12 and HC when using the micronucleus assay for human biomonitoring studies.
Vitamin B12 Deficiency
Mean intake by ethnic group (mg)20 yrs 40 yrs 60 yrs
RDA 2.4 2.4 2.4
White 6.8 6.9 6.3Black 7.2 6.2 5.2Hispanic 6.3 5.6 6.1
Mean intake by ethnic group (mg)20 yrs 40 yrs 60 yrs
RDA 2.4 2.4 2.4
White 3.7 3.7 4.1Black 5.3 3.9 3.8Hispanic 4.2 3.6 3.4
. Each of the six dependent variables (that were analyzed by nonlinear regression in former figures) were transformed to Z scores and modeled as a quadratic function of the ln-liver nonheme iron as the independent variable. The equation for the RCR ratio's Z score was obtained from inverted RCR values (1/RCR) so that normal rats had the lower instead of the higher values. For presentation purposes each model line was obtained from 9 values of liver iron. All statistics were performed as in materials and methods.
Analysis of nonlinear regression models: comparison of an overall model and individual models of Z-transformed values vs. ln-
nonheme liver iron
Over allDCF-PMNsDCF-LymphRh123-PMNsRh123-LymphmtDNA damage1/RCR
-1.5
-1
-0.5
0
0.5
1
1.5
2
2.5
3
-1.5 -1 -0.5 0 0.5 1 1.5 2 2.5
LN nonheme Fe (µmol/g wet liver)
Z sc
ore
normal
Succ-CoA + GlyALA
2ALA
PBGPorphyrins
Cytosol
PPIX PPGIX
Heme-b
FeII
MitochondriaFC
Synthesis of Heme
Heme-a
PLP
ALA
CH
CH2
CH2
CH2
COOH COOH
CH2
CH2
CH3
CH3
H3C
Fe
N N
N N
CH CH
CH
CH
H3C
CH
CH2
(1) Farnesylation
(2) Oxidation
Heme-b Heme-a(Only in complex IV)
Maturation of heme-b to heme-a is rate limiting for the assembly of complex IV
Micronutrient requirements for heme synthesis
[++][++]Pantothenate
[++]Lipoic acid++++++Biotin
[++][++]Copper++++++++Iron
Riboflavin+++++?+?Zinc
++[++]Pyridoxine
DNA damage
Oxidative stress
Complex IVHeme-aMicronutrient
++ = Atamna/Ames [++] Literature
0.0 2.5 5.0 7.5 10.0 12.5 15.020253035404550556065
cdFBS-BD
nFBS-BSnFBS-+B--BS
Weeks
cdFBS+B-BS
Biotin deficiency accelerates cell senescence
9) Atamna et al (2001) JBC. 10) Atamna et al (2002) ABB.
Similarity Between the Consequences of Heme Deficiency and Normal
Aging/neurodegenerationFactor in Study Heme Deficiency Aging/Neurodegeneration
Complex IVIronOxidative StressAPP
NOSCell-cycle anddifferentiationMetabolismCalciumFerrochelataseHeme synthesis
Loss of complex IVAccumulationIncreased Decreased andaggregate appearIncreasedDisabled differentiationor proliferationMitochondrial declineCorruptedIncreasedDecreased
Loss of complex IVAccumulationIncreaseddimmer or aggregate
IncreasedLoss of Axons; neuronal deathHypometabolismCorruptedIncreased in senescent cellsDecreased with age**
*
*Not Determined in vivo. **Not determined in the aging brain
1994-96, 1998 CSFII Study, USDA
“The main distinguishing characteristicbetween man and the lower animals
is the desire to take pills”
Mark Twain
The Economist, December 13, 2003
Dr. Allen Spiegel, NIDDK/NIH
Energy Sources - 1999-2000Food
1. Regular soft drinks 7.1
2. Cake, sweet rolls, doughnuts, pastries 10.6
3. Hamburgers, cheeseburgers, meatloaf 13.8
4. Pizza 16.8
5. Potato chips, corn chips, popcorn 19.7
6. Rice 22.4
7. Rolls, buns, English muffins, bagels 25.0
8. Cheese or cheese spread 27.6
9. Beer 30.2
10. French fries, fried potatoes 32.4
Gladys Block from National Health and Nutrition Examination Survey (NHANES) 2000.
Cumulative Percentage
THE SEARCH FOR THE WEAPONSOF MASS REDUCTION
“Things sweet to taste prove in digestion sour.”
Shakespeare (King Richard the Second)
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