The TRUE STORY - Shellfish Association of Great Britain · The Context of a Scientific Story Fact=...

38
Omega Fatty Acids and Cholesterol – The TRUE STORY Bill Lands http://efaeducation.nih.gov/ http://ods.od.nih.gov/eicosanoids Fish, Omega-3 and Human Health Fishmonger’s Hall – May 23, 2006

Transcript of The TRUE STORY - Shellfish Association of Great Britain · The Context of a Scientific Story Fact=...

Page 1: The TRUE STORY - Shellfish Association of Great Britain · The Context of a Scientific Story Fact= a truth known by actual experience Fiction= an imaginative narration; =allegation

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

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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

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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

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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)

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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

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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

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From: http://efaeducation.nih.gov/sig/beginners.html

BalancingEssential Fats in

Foods63

Promotes Healthand

Prevents Disease

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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

.

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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

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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

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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

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From: http://efaeducation.nih.gov/sig/beginners.html

Choose foods that balancebalancethe 6’s6’s and the 3’s3’s

in your body

36

.

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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

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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

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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

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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

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KIM-2 shows you the milligrams of different fatty acids

Free software at http://efaeducation.nih.gov/sig/kim.html

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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

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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

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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

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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

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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

3

4

1

2

3

4

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0

5

10

15

20

25

30

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

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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!)

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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

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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.

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2005

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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.

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Joseph R. Hibbeln, MD re: 2004 FDA-EPA methyl mercury seafood advisory

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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 )

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%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

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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

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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

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(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

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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