the true story - shellfish association of great britain · the context of a scientific story fact=...
TRANSCRIPT
Omega Fatty Acids and Cholesterol –
The TRUE STORY
Bill Landshttp://efaeducation.nih.gov/
http://ods.od.nih.gov/eicosanoidsFish, Omega-3 and Human Health
Fishmonger’s Hall – May 23, 2006
The Context of a Scientific StoryFact= a truth known by actual experience
Fiction= an imaginative narration; =allegation that a fact exists which is known not to exist; =a story invented to deceive
Oversimplified = To simplify to the point of causing misrepresentation, misconception, or error
Paradox= an opinion contrary to received opinion; =an apparent self-contradiction that is explained by added truthful information
Balance= to estimate relative importance or weight
Adventure= a hazardous enterprise of uncertain outcome; =an exciting experience
Heart damage starts in childhood
0
10
20
30
40
50
60
0 10 20 30 40 50 60 70 80 90
Age (yrs) .
Inju
red
surf
ace
(%)
abdominal aortacoronary arteryHeart attacks/1000
PDAY results, Art.Thromb.Vasc.Biol.19:753-761(1999)
Start HereFor PrimaryPrevention
see page 15 in Morgan County Menus
Food + appetiteVitamins & mineralsCarbohydratesProteins (some essential amino acids)Fats (some essential fatty acids)
Metabolites that burn to CO2 + H20+
Unburned Metabolites
Stored tissue products = YOU
(upstream)
+ exercise
are converted to
Lifeappetite=pages 4-5 in Morgan County Menusexercise=pages 18-21 in Morgan County Menus (downstream)
Biomarker
Biomarker
Biomarker
Excess Fats+ Food Energy
High CytosolicAcetyl-CoA
+ NAD(P)H
CytosolicHMG-CoA
High Plasma Cholesterol
LiverCholesterol
Fat Synthesis+ VLDL Secretion
Isoprenoids
Mevalonate
PrenylatedProteinsInflammatory cytokines
& Proliferation
InflammatoryVascular WallPlaques
Fast Formation
ThrombosisArrhythmia
Morbidity &Mortality
Reactive oxygen species
Ischemia
PlateletActivation
Synthesisof
Nitric oxide
Statins
HMG-CoAReductase
High PlasmaTriglycerides
+ NEFA
TransientPostprandialOxidant Stress
Nitroglycerin
Diet-induced Dyslipidemias and Disease
????
PrimaryPrevention
PREVENTPREVENTTHIS CAUSE THIS CAUSE ––
LEARN APPETITE LEARN APPETITE CONTROLCONTROL
Obesity &Type2 diabetes
appetite=pages 4 & 5 in Morgan County Menus
Biomarker
n-6Eicosanoids
Inflammatory cytokines& Proliferation
InflammatoryVascular WallPlaques
Fast Formation
Low n-3 fatsin the diet
Phospholipase
High % n-6 in HUFA of tissue phospholipids
ThrombosisArrhythmia
Morbidity &Mortality
Reactive oxygen species
Ischemia
PlateletActivation
Synthesisof
Nitric oxide
Nitroglycerin
Aspirin
Diet-induced Dyslipidemias and DiseasePrimaryPrevention PREVENTPREVENT
THIS CAUSE THIS CAUSE –– LEARN FOOD CHOICESLEARN FOOD CHOICES
foods=pages 30-37 in Morgan County Menus
From: http://efaeducation.nih.gov/sig/beginners.html
BalancingEssential Fats in
Foods63
Promotes Healthand
Prevents Disease
From: http://efaeducation.nih.gov/sig/beginners.html
A Balanc e d Re s po ns e is Ne e de dVitamin-like ===========>>> Ho rmo ne-like e ssentia l fa ts metabolized to e icosanoidsFOOD > short 3 ===>> long 3 =======>> 3-e ic o s ===>> mo derate res pons esFOOD > metabolized to me tabolized to FOOD > short 6 ===>> long 6 =======>> 6-e ic o s ===>> vig o ro us re s po ns e s
Short 3 makes long 3
long 3 makes 3-eicos
3-eicos make responses
.
From: http://efaeducation.nih.gov/sig/beginners.html
A Balanc e d Re s po ns e is Ne e de dVitamin-like ===========>>> Ho rmo ne-like e ssentia l fa ts metabolized to e icosanoidsFOOD > short 3 ===>> long 3 =======>> 3-e ic o s ===>> mo derate res pons esFOOD > metabolized to me tabolized to FOOD > short 6 ===>> long 6 =======>> 6-e ic o s ===>> vig o ro us re s po ns e s
Short 6 makes long 6
long 6 makes 6-eicos
6-eicos make responses
From: http://efaeducation.nih.gov/sig/beginners.html
A Balanc e d Re s po ns e is Ne e de d
Make balanc e d food c ho ic e s !Exc e s s ive 6-e ic o s o c c ur in: Heart attacks
StrokesThrombos isArrhythmiaArthritisAs thmaMens trual crampsHeadachesTumor metas tas es
Vitamin-like ===========>>> Ho rmo ne-like e ssentia l fa ts metabolized to e icosanoidsFOOD > short 3 ===>> long 3 =======>> 3-e ic o s ===>> mo derate res pons esFOOD > metabolized to me tabolized to FOOD > short 6 ===>> long 6 =======>> 6-e ic o s ===>> vig o ro us re s po ns e s
Conditions for which you take aspirin, ibuprofen(Motrin),
acetominophen(Tylenol),COX-2 blockers, & NSAID’s
all have excessive 6-eicosanoids
Eicosanoids Differ
6
3
Sorry 3.I don’t want to hurt people.
I can cut
excess 6 actions!
From: http://efaeducation.nih.gov/sig/beginners.html
Eicosanoids Differ
6
3
Sorry 3.I don’t want to hurt people.
I can cut
excess 6 actions!
From: http://efaeducation.nih.gov/sig/beginners.html
NUTRITION helps inNUTRITION helps in
PREVENTIONPREVENTION ofof
what gets what gets TREATMENTTREATMENT
with DRUGSwith DRUGS
From: http://efaeducation.nih.gov/sig/beginners.html
Choose foods that balancebalancethe 6’s6’s and the 3’s3’s
in your body
36
.
CHD Mortality and Tissue HUFA
y = 3.0323x - 74.8R2 = 0.9866
0
50
100
150
200
20 30 40 50 60 70 80% n-6 HUFA in Total HUFA
CH
D M
orta
lity
Greenland
Japan Quebec Inuit
Quebec Cree
USA
Quebec Urban
HUFA imbalance is a diet-induced dyslipidemiaHUFA are long-chain highly unsaturated fatty acids
Crete Spain Padova
Diversity in Tissue HUFA
20
30
40
50
60
70
80
20 30 40 50 60 70 80
Diet-Based Values
%n-
6HU
FA in
Tot
al H
UFA
Ass
ayed
Predicted
Lands, Current Topics in Nutraceutical Res. 1: 113-120, 2003
A handy calculator for planning clinical trials is at:http://efaeducation.nih.gov/dietbalance.html
DIET PREDICTS HUFA PROPORTIONS IN PLASMATrial Typical dietsDiet USAMeditJapan
AVERAGE DAILY DIETARY INTAKES en% 18:3n-3 > 1.00 0.85 0.60 0.76 (short 3)en% 18:2n-6 > 2.00 6.82 2.30 5.04 (short 6)en% n-3 HUFA 0.20 0.03 0.09 0.54 (long 3)en% n-6 HUFA 0.08 0.08 0.08 0.08 (long 6) PREDICTED% n-6 in HUFA 47 80 62 51
<<<Eat less<<<Eat more
Advice for USA
<<<Cut risk
An equation predicting HUFA dyslipidemia is at:http://efaeducation.nih.gov/hufacalc.html
Like ly Mortality Ris k from HUFA Dys lipidemia(Dea ths per 100,000 popula tion)
en% 18:2n-6>> 1 2 3 4 5 6 7 8 9 10en%H3 0.03 86 124 143 154 161 166 169 172 175 177en%H3 0.10 58 99 121 135 144 151 156 160 164 166en%H3 0.20 33 73 97 113 124 133 140 145 149 153en%H3 0.30 17 54 78 95 108 118 125 132 137 141en%H3 0.40 6 40 64 81 94 105 113 120 126 131en%H3 0.50 -2 30 52 69 83 93 102 110 116 121en%H3 0.60 -8 21 43 59 73 84 93 100 107 112en%H3 0.90 -21 3 21 37 49 60 69 77 84 90en%H3 1.20 -29 -9 7 21 33 43 52 60 67 73
bas ed on CHD deaths per 100,000 = 3 x (%n-6HUFA in HUFA) - 75& die t-tis s ue pattern at http://e faeducation.nih.gov/s ig /hufacalc .html
Eat less omega-6Eat more omega-3
Cut risk in half
Cut BOTH and predict preventing most CHD
Free software at http://efaeducation.nih.gov/sig/kim.html
KIM-2 shows you the milligrams of different fatty acids
Free software at http://efaeducation.nih.gov/sig/kim.html
Keep the calories under control
Balance the eicosanoid precursorsin your body
Use KIM-2 toPrevent Imbalances in Two Easily Adjusted Food Choices
Free software at http://efaeducation.nih.gov/sig/kim.html
A handy calculator for planning clinical trials is at:http://efaeducation.nih.gov/dietbalance.html
DIET PREDICTS HUFA PROPORTIONS IN PLASMAUSA shellfish Food oyster mussel crab beef pork
AVERAGE DAILY INTAKES en% 18:3n-3 > 1.00 0.28 0.08 0.05 1.03 0.05 (short 3)en% 18:2n-6 > 6.00 0.10 0.03 0.04 2.01 2.07 (short 6)en% n-3 HUFA 0.03 1.06 0.70 0.71 0.01 0.01 (long 3)en% n-6 HUFA 0.08 0.14 0.11 0.11 0.03 0.12 (long 6) PREDICTED% n-6 in HUFA 78 14 11 12 58 84
An equation predicting HUFA dyslipidemia is at:http://efaeducation.nih.gov/hufacalc.html
Free software at http://efaeducation.nih.gov/sig/kim.html
A “healthy??” recipe for Sesame Ginger Chicken:
organic extra virgin olive or macadamia nut oil (1tsp for coating)4 chicken breasts (6 oz. each)5 green onions, cut into 2" shreds, reserving 1/4 cup shreds 1/3 cup chopped fresh cilantro (or1.5 Tablespoons dried cilantro) 1 lemon, cut into 8 thin slices 2 Tablespoons dark sesame oilTeaspoon hot chili oil (optional) 2 Tablespoons minced and packed ginger 1/3 cup sake or dry sherry 1/4 cup light soy sauceFour servings have a total of:1tsp = 356mg18ω6 +27mg18ω324oz =4.06g18ω6 +0.21g18ω3+0.42g20ω6+0.26g20/22ω32Tbsp=11.2g18ω6 +82mg18ω3 1tsp=?=1.86g18ω6 +14mg18ω31serving=4.37g18ω6 +83mg18ω3+0.10g20ω6+65mg20/22ω3
Overall, this predicts 80%ω6 in HUFA
1
2
3
4
1
2
3
4
A “healthy?” recipe for Sesame Ginger Shrimp:
organic extra virgin olive or macadamia nut oil (1tsp for coating)24oz steamed, peeled shrimp (4 servings, 6oz.@) 5 green onions, cut into 2" shreds, reserving 1/4 cup shreds 1/3 cup chopped fresh cilantro (or1.5 Tablespoons dried cilantro) 1 lemon, cut into 8 thin slices 2 Tablespoons dark sesame oilTeaspoon hot chili oil (optional) 2 Tablespoons minced and packed ginger 1/3 cup sake or dry sherry 1/4 cup light soy sauceFour servings have a total of:1tsp = 356mg18ω6 +27mg18ω324oz =144mg18ω6 +80mg18ω3+0.48g20ω6+2.28g20/22ω32Tbsp=11.2g18ω6 +82mg18ω3 1tsp=?=1.86g18ω6 +14mg18ω31serving=3.39g18ω6 +51mg18ω3+0.12g20ω6+0.57g20/22ω3
Overall, this predicts about 64%ω6 in HUFA
1
2
3
4
1
2
3
4
A healthier recipe for Spicy Ginger Shrimp:
organic extra virgin olive or macadamia nut oil (1tsp for coating)24 oz. steamed, peeled shrimp (4 servings, 6oz.@)5 green onions, cut into 2" shreds, reserving 1/4 cup shreds 1/3 cup chopped fresh cilantro (or1.5 Tablespoons dried cilantro) 1 lemon, cut into 8 thin slices 1 Tablespoon olive oil0.5 Teaspoon hot tabasco sauce (optional) 2 Tablespoons minced and packed ginger 1/3 cup sake or dry sherry 1/4 cup light soy sauceFour servings have a total of:1tsp = 356mg18ω6 +27mg18ω324oz=144mg18ω6 +80mg18ω3+0.48g20ω6+2.28g20/22ω31Tbsp=1.07g18ω6 +81mg18ω3 0.5tsp= 9mg18ω6 +0mg18ω31 serving=0.39g18ω6 +47mg18ω3+0.12g20ω6+0.57g20/22ω3Overall, this predicts about 35%ω6 in HUFA
1
2
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4
1
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4
0
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15
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25
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35
100 150 200 250 300 350
Serum TC (mg/dl)
25-y
r.CH
D m
orta
lity
(%)
No.Europe-80%
USA-75%
Serbia-65%
So.Europe-60%
Crete-50%
Japan-40%
0
5
10
15
20
25
30
35
100 150 200 250 300 350Serum TC (mg/dl)
25-y
r.CH
D m
orta
lity
(%)
No.Europe
USA
Serbia
So.Europe
Crete
Japan
JAMA 274: 131-136 (1995 )
TC biomarker poorly predictsthe absolute CHD mortality seen in the Seven Countries Study
TC biomarker predicts CHD death only to the degree that an omega-6 inflammatory biomarker is >40%
%n-6inHUFA
We can predict all the results with:CHD =3+3(%n-6inHUFA-40)(TC-100)/1000Observed 25-yr CHD death rates
WHEN omega-3 slowed omega-6 inflammation & thrombosis, diet imbalances causing mevalonate and isoprenoid formation
were NOT fatal.
see page 16-17 in Morgan County Menus
NIH Consensus Conference, Dec. 10-12, 1984
Panel “Conclusion”Elevated blood cholesterol level is a major cause of coronary artery
disease.” (This was a tragic fiction!)
Panel advice on “How should adults with hypercholesterolemia be treated?”“The first step in treatment of persons with high-risk and moderate-
risk blood cholesterol levels is diet therapy and caloric restriction for weight normalization in the overweight. Weight loss may reduce blood cholesterol levels, and a moderate level of physical exercise may be helpful in this regard. The dietary approach should be to lower total fat, saturated fat and cholesterol consumption.”
“Drug therapy should be used only after a careful trial of diet modification using the most rigorous diet appropriate for the particular individual. Even when use of drugs seems appropriate, it is important to stress that maximal diet therapy should be continued.”
(Poor focus on diet advice over 25 years led to epidemics of obesity andstatin use plus continuing events mediated by excessive omega-6 actions!)
Biomarker
Biomarker
Excess Fats+ Food Energy
High CytosolicAcetyl-CoA
+ NAD(P)H
CytosolicHMG-CoA
High Plasma Cholesterol
LiverCholesterol
Fat Synthesis+ VLDL Secretion
Isoprenoids
Mevalonaten-6
Eicosanoids
PrenylatedProteinsInflammatory cytokines
& Proliferation
InflammatoryVascular WallPlaques
Fast Formation
Low n-3 fatsin the diet
Phospholipase
High % n-6 in HUFA of tissue phospholipids
ThrombosisArrhythmia
Morbidity &Mortality
Reactive oxygen species
Ischemia
PlateletActivation
Synthesisof
Nitric oxide
Statins
HMG-CoAReductase
High PlasmaTriglycerides
+ NEFA
TransientPostprandialOxidant Stress
Nitroglycerin
Aspirin
Diet-induced Dyslipidemias and Disease
????
PrimaryPrevention
Biomarker
Obesity &Type2 diabetes
Biomarker
see pages 14 & 17 in Morgan County Menus
Bill Lands (1930-present)
retired from Univ. Michigan (Ann Arbor, 1955-1980), & Univ. Illinois (Chicago, 1980-1990),
&Natl. Institutes of Health (Bethesda, 1990-2002) and now is on Board of Directors, Omega Protein Corp.
2005
Nicholas V.C. Ralston, Dec.2005 talk
MOLAR RATIOS OF Hg:Se
0
1
2
3
4So
le
Flou
nder
Salm
on
Tuna
Pollo
ck
Hal
ibut
Cod
Snap
per
Gro
uper
Swor
dfis
h
US
aver
age
Pilo
t Wha
le
Hg:
Se m
olar
rat
io
WHEN selenium is sufficient to suppress mercury’s actions, dietary mercury that increases tissue levels is still NOT toxic.
Joseph R. Hibbeln, MD re: 2004 FDA-EPA methyl mercury seafood advisory
Tissue HUFA are maintained by dietary PUFAan empirical hyperbolic metabolic relationship
=1 +1 +1 +1 + HC6
en%H6en%H3
HC3
PC6en%P6
en%P3 en%H3 en%O en%P6PC3 HI3 CO Ks
++++ )()(
10010020:3+20:4n-6in HUFA
HC3 = 3.0 HC6 = 0.70 PC3 = 0.0555 PC6 = 0.0441HI3 = 0.005 HI6 = 0.040 C0 = 5.0 Ks = 0.175
Lands et al, BBA 1180: 147-162 (1992)[constants revised in 2002]
( http://efaeducation.nih.gov/sig/hufacalc.html )
%n-3 HUFA (in total HUFA) by Ethnic Group & Age
45
54
61
19 20
35
2921 25
0
10
20
30
40
50
60
70
80
90
0 2 4 6 8 10 12 1 8-34 35-49 50 + 18-34 35-49 50 + 18-34 35-49 50 + Quebec Cree Inuit
66 CHD/100,000
93 CHD/100,000
140 CHD/100,000
What are major human disabilities?Disability-adjusted life year = DALY Projected types of DALYs in 2020
Rank Worldwide Developed NationsDisease or Injury DALYs Cum.% Disease or Injury DALYs Cum.%All causes 1389 All causes 161
1 Ischemic Heart disease 82 6 Ischemic Heart disease 18 112 Unipolar major depression 79 12 Cerebrovascular disease 10 173 Road traffic accidents 71 17 Unipolar major depression 10 234 Cerebrovascular disease 61 21 Lung and throat cancers 7 285 Chronic pulmonary disease 58 25 Road traffic accidents 7 326 Lower respiratory infections 43 28 Alcohol abuse 6 36 7 Tuberculosis 43 31 Osteoarthritis 5 408 War injuries 41 34 Dementia & CNS disorders 5 439 Diarrheal diseases 37 37 Chronic pulmonary disease 5 4610 HIV-AIDS 36 40 Self-inflicted injuries 4 48
CJL Murray & AD Lopez, Lancet 1997; 349: 1498–1504
A B C D
E
F G H
HUFA are 20- and 22-carbon highly unsaturated fatty acids with >3 double bonds
Biomarkers of n-6HUFA status in tissues are:%n-6 HUFA in HUFA = 100*(A+B+C)/(A+B+C+D+E+F+G+H) %n-6 HUFA in FA = 100*(A+B+C)/(A+B+C+D+E+F+G+H+J+K+L+M+N+O+P)
J K
L MN
OP
#2. HUFA result from elongation & desaturation
longshort
(Learning sites & KIM-2 software are on County Library computers)
Distance learning websitesfor essential fatty acids and eicosanoids
http://ods.od.nih.gov/eicosanoids/
http://efaeducation.nih.gov/
For Primary Prevention of Chronic Disease -Plan Daily Menus that Balance Tissue HUFA
Using Personal Interactive Software, KIM-2http://efaeducation.nih.gov/sig/kim.html
Understanding Causes & Consequences
How does an event happen?omega-6 HUFA give inflammation, thrombosis & arrhythmiaomega-3 HUFA slow actions of omega-6 HUFA
What is a consequence of an event happening?inflammation, thrombosis & arrhythmia cause deathfood choices cause tissue HUFA proportions
Why do we intervene in an event happening?preventing a cause helps more than treating its consequence
See pages 1-40 in Morgan County Menus - and be a FASTlearner