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  • 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

  • The Context of a Scientific Story Fact= 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) .

    In ju

    re d

    su rf

    ac e

    (% )

    abdominal aorta coronary artery Heart attacks/1000

    PDAY results, Art.Thromb.Vasc.Biol.19:753-761(1999)

    Start Here For Primary Prevention

    see page 15 in Morgan County Menus

  • Food + appetite Vitamins & minerals Carbohydrates Proteins (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 Menus exercise=pages 18-21 in Morgan County Menus (downstream)

  • Biomarker

    Biomarker

    Biomarker

    Excess Fats + Food Energy

    High Cytosolic Acetyl-CoA

    + NAD(P)H

    Cytosolic HMG-CoA

    High Plasma Cholesterol

    Liver Cholesterol

    Fat Synthesis + VLDL Secretion

    Isoprenoids

    Mevalonate

    Prenylated ProteinsInflammatory cytokines

    & Proliferation

    Inflammatory Vascular Wall Plaques

    Fast Formation

    Thrombosis Arrhythmia

    Morbidity & Mortality

    Reactive oxygen species

    Ischemia

    Platelet Activation

    Synthesis of

    Nitric oxide

    Statins

    HMG-CoA Reductase

    High Plasma Triglycerides

    + NEFA

    Transient Postprandial Oxidant Stress

    Nitroglycerin

    Diet-induced Dyslipidemias and Disease

    ????

    Primary Prevention

    PREVENTPREVENT THIS CAUSE THIS CAUSE ––

    LEARN APPETITE LEARN APPETITE CONTROLCONTROL

    Obesity & Type2 diabetes

    appetite=pages 4 & 5 in Morgan County Menus

  • Biomarker

    n-6 Eicosanoids

    Inflammatory cytokines & Proliferation

    Inflammatory Vascular Wall Plaques

    Fast Formation

    Low n-3 fats in the diet

    Phospholipase

    High % n-6 in HUFA of tissue phospholipids

    Thrombosis Arrhythmia

    Morbidity & Mortality

    Reactive oxygen species

    Ischemia

    Platelet Activation

    Synthesis of

    Nitric oxide

    Nitroglycerin

    Aspirin

    Diet-induced Dyslipidemias and DiseasePrimary Prevention 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

    Balancing Essential Fats in

    Foods 63

    Promotes Health and

    Prevents Disease

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

    A Balanc e d Re s po ns e is Ne e de d Vitamin-like ===========>>> Ho rmo ne-like e ssentia l fa ts metabolized to e icosanoids FOOD > short 3 ===>> long 3 =======>> 3-e ic o s ===>> mo derate res pons es FOOD > 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 d Vitamin-like ===========>>> Ho rmo ne-like e ssentia l fa ts metabolized to e icosanoids FOOD > short 3 ===>> long 3 =======>> 3-e ic o s ===>> mo derate res pons es FOOD > 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

    Strokes Thrombos is Arrhythmia Arthritis As thma Mens trual cramps Headaches Tumor metas tas es

    Vitamin-like ===========>>> Ho rmo ne-like e ssentia l fa ts metabolized to e icosanoids FOOD > short 3 ===>> long 3 =======>> 3-e ic o s ===>> mo derate res pons es FOOD > 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 balancebalance the 6’s6’s and the 3’s3’s

    in your body

    36

    .

  • CHD Mortality and Tissue HUFA

    y = 3.0323x - 74.8 R2 = 0.9866

    0

    50

    100

    150

    200

    20 30 40 50 60 70 80 % n-6 HUFA in Total HUFA

    C H

    D M

    or ta

    lit y

    Greenland

    Japan Quebec Inuit

    Quebec Cree

    USA

    Quebec Urban

    HUFA imbalance is a diet-induced dyslipidemia HUFA 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-

    6H U

    FA in

    T ot

    al H

    U FA

    A ss

    ay ed

    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 PLASMA Trial Typical diets Diet 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

  • 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 10 en%H3 0.03 86 124 143 154 161 166 169 172 175 177 en%H3 0.10 58 99 121 135 144 151 156 160 164 166 en%H3 0.20 33 73 97 113 124 133 140 145 149 153 en%H3 0.30 17 54 78 95 108 118 125 132 137 141 en%H3 0.40 6 40 64 81 94 105 113 120 126 131 en%H3 0.50 -2 30 52 69 83 93 102 110 116 121 en%H3 0.60 -8 21 43 59 73 84 93 100 107 112 en%H3 0.90 -21 3 21 37 49 60 69 77 84 90 en%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 precursors in your body

    Use KIM-2 to Prevent 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 PLASMA USA 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

    Fre