Omega-3 Fatty Acids in Critical Illness: Mechanisms and Clinical Applications: When disease is prevented, treatment costs are not needed

Transcription

1 Omega-3 Fatty Acids in Critical Illness: Mechanisms and Clinical Applications: When disease is prevented, treatment costs are not needed Bill Lands, PhD Fellow AAAS, ASN, SFRBM My initial research on humans was funded by an unrestricted award from Pfizer Inc. I am a stockholder and non-employee member of the board of directors of Omega Protein Inc.

2 Nutrition Support Therapy is part of nutrition therapy which is a component of medical treatment that can include oral, enteral, and parenteral nutrition to maintain or restore optimal nutrition status and health.

3 Balance in the Tissue is the Issue Incorporation & Washout Found = 5111 Enteral Parenteral Potential studies Studies included 27 9 Clinical Effects Found = 2921 Enteral Parenteral Potential studies RCTs included Concluded beneficial effects of n-3fa supplementation BS vandermeij et al, Am.J.Clin.Nutr. 2011; 94: See also meta-analysis of parachutes: GCS Smith and JP Pell, Brit Med J. 2003; 327: 1459

4 OPTIMAL NUTRITION STATUS means: much chronic disease prevented many treatments not needed Know Your Numbers 1. Your food s Omega-3 Balance Scores 2. Your blood s %omega 3 in HUFA 3. Your annual healthcare claim costs Know Their Context

5 USDA Nutrient Database lists fatty acids in foods Use 11 n-3 & n-6 acids to form one value of Omega-3 Balance Score Finger-tip blood-spot assay lists fatty acids in blood 14: Myristic 14: Myristic 14: Myristoleic 14: Myristoleic 15: Pentadecanoic 15: Pentadecanoic 15: : : Palmitic 16: Palmitic 16:1w :1w :1w Palmitoleic 16:1w Palmitoleic 17: Heptadecanoic 17: Heptadecanoic 17: : : Stearic 18: Stearic 18:1w Oleic 18:1w Oleic 18:1w Vaccenic 18:1w Vaccenic 18:1w :1w :2w Linoleic (LA) 18:2w Linoleic (LA) 18:3w gamma-linolenic (GLA) 18:3w gamma-linolenic (GLA) 18:3w alpha-linolenic (ALA) 18:3w alpha-linolenic (ALA) 18:4w Stearidonic (SDA) 18:4w Stearidonic (SDA) 20: Arachidic 20: Arachidic 20:1w :1w :1w :1w :2w Eicosadienoic 20:2w Eicosadienoic 20:3w Mead's acid 20:3w Mead's acid 20:3w Dihomogammalinolenic (DGLA) 20:3w Dihomogammalinolenic (DGLA) 20:4w Arachidonic (AA) 20:4w Arachidonic (AA) 20:3w Eicosatrienoic (n-3) 20:3w Eicosatrienoic (n-3) 20:4w Eicosatetraenoic (n-3) 20:4w Eicosatetraenoic (n-3) 20:5w Eicosapentaenoic (EPA) 20:5w Eicosapentaenoic (EPA) 22: Behenic 22: Behenic 22:1w Erucic 22:1w Erucic 22:4w Docosatetraenoic 22:4w Docosatetraenoic 22:5w Docosapentaenoic (n-6) 22:5w Docosapentaenoic (n-6) 22:5w Docosapentaenoic (n-3) 22:5w Docosapentaenoic (n-3) 24: Lignoceric 24: Lignoceric 22:6w Docosahexaenoic (DHA) 22:6w Docosahexaenoic (DHA) Use 8 n-3 & n-6 HUFA to form one value of %Omega-3 in HUFA

6 Omega-3 Balance Scores Coho salmon Beef steak Crab Pork Chicken Turkey

7 From Vitamins to Hormones: Competition is the Context OMEGA-3 OMEGA-6 Linolenic acid (18:3n-3) ALA Linoleic acid (18:2n-6) LA Stearidonic acid (18:4n-3) Gamma-linolenic acid (18:3n-6) Dihomoγlinolenate (20:3n-6) DGLA Eicosapentaenoic (20:5n-3)EPA Arachidonic acid (20:4n-6) AA HUFA make hormones DPA (22:5n-3) Adrenic Acid (22:4n-6) Docosahexaenoic (22:6n-3) DHA DPA (22:5n-6) Highly Unsaturated Fatty Acids (HUFA) have 20- and 22-carbons & 3 or more double bonds

8 When disease is prevented, treatment costs are not needed Every year excess actions of omega-6 at tissue receptors cause financial loss for people & corporations & the nation Medical & Pharmacy cost Health-related Absenteeism & Presenteeism loss with an Overall loss = employee $5,184 $10,000 $15, thousand employees $51,840,000 >millions $152,000,000 >millions 150 million employees $777,000,000,000 >billions $2,250,000,000,000 >trillions If we can prevent half of this, why don t we?

9 FOOD amino acids nucleosides fatty acids sugars essential FA Connecting the primary cause to its consequences We store vitamin-like omega-3 and omega-6 acids as hormone precursors (HUFA) that form hormones acting on tissue receptors <<Omega-3 Balance Score average Biomarker <<This is a valid surrogate endpoint for nutrition-based % n-6 in HUFA of primary prevention of CHD morbidity & mortality tissue phospholipids n-3 & n-6 HUFA release aspirin XS n-6 eicosanoids platelet activation vessel wall plaques thrombosis ischemia arrhythmia oxidant stress & inflammation & proliferation & impaired nitric oxide Morbidity & Mortality arthritis asthma colon cancer length of hospital stay psychiatric disorders workplace disruption health care $$ claims

10 Eicosanoids Wada et al., J Biol Chem. 2007; 282(31):: Tissue HUFA Relative n-3 & n-6 actions with enzymes & receptors 3 Differ Anything 3 can do I can do better! Release HUFA Oxidize HUFA to intermediates Overall, n-3 forms act less intensely than n-6 forms. Good grief! Sometimes 6 is just too much! 6 Make hormones Hormone receptor actions

11 Heart CHD Attack Mortality Death Rate Americans have high omega-6 in HUFA & an omega-3 deficit CHD Mortality and Tissue HUFA y = x R 2 = Quebec Cree USA Quebec Urban $3,930/yr $3,052/yr WV-PEIA=$6,408 Health Claim Cost USA=$5,184/yr = MRFIT quintiles 50 0 Japan Greenland $2,076/yr Quebec Inuit % n-6 HUFA in Total HUFA % omega-6 in HUFA Relative risk - - Siscovick,1995 & Alberts, 2002 When disease is prevented, treatment costs are not needed.

12 location location %HUFA %HUFA %6inH %6inH troit Detroit ltimore-2008 Baltimore ebecer-2001 Quebecer IC study-2007 ARIC study troit-2005 Detroit lumbus, Columbus, avg. = avg. 15= Foods in North America have an excess of n-6 over n-3 fats and cause accumulation of a high percent of n-6 in HUFA.

13 Diverse Food Habits and Tissue Consequences Average daily menu balance Related %omega3 in HUFA 72% 67% 62% 57% 52% 47% 42% 37% 32% 27% 22% 17% 12% Related %omega6 in HUFA 28% 33% 38% 43% 48% 53% 58% 63% 68% 73% 78% 83% 88%

14 We started with lots of -7 values We changed to lots of -3 Blood Assay value Likely Likely daily average Blood Assay value Likely Likely daily average Team %n-3inh food habit Omega-3 Balance Score Team %3inH food habit Omega-3 Balance Score Member February data Member May data G 52 typical 0 Related Health G 67 traditional 2 P 50 middle-aged -1 Claim Cost P 64 Japanese 2 Related Health I 48 Japanese -1 $???? I 55 0 Claim Cost L 44-2 A 51-1 J 34 typical -4 $2,076 L 51 typical -1 O 33 Mediterranian -4 O 50 middle-aged -1 H 30-5 $3,052 Y 47 Japanese -1 $???? C 29-5 H 41-2 N 26 typical -5 R 40-3 A 25 European -5 $3,930 V 40-3 V 25-5 T 39-3 $2,076 W 23-6 F 38-3 S 22 typical -6 J 37-3 E 22 American -6 $5,184 K 36-3 U 21-6 N 35 typical -4 $3,052 Q 21-6 S 30 Mediterranian -4 X 19 typical -7 W 27-5 K 17 West -7 $6,408 B 27 typical -5 $3,930 B 16 Virginian? -7 E 26 European -5 M 16-7 M 25-5 D 15-7 U 25-5 F 15-7 D 23-6 $5,184 Y 15-7 Q 22 typical -6 R 15-7 X 21 American -6 T 12-8 C 21-6 $6,408

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16 Omega-3 Balance Scores Coho salmon Beef steak Crab Pork Chicken Turkey

17 Rye Rice Barley Wheat Kellog s Corn Flakes Corn Buckwheat Oatmeal Flax meal Quinoa

18 Parenteral Foods and Their Balance Scores Omegaven (10%) + 49 Lipoven (10%) - 9 Lipoplus (20%) + 7 Intralipid (20%) - 20 Diverse Food Habits and Tissue Consequences Average daily menu balance Related %omega6 in HUFA 28% 33% 38% 43% 48% 53% 58% 63% 68% 73% 78% 83% 88%

19 Effective Primary Prevention Needs You Tools for Primary Prevention When disease is prevented, TO UNDERSTAND treatment costs are not needed Low-cost Food energy assay causes of transient %n-6 tissue in HUFA insults to monitor risk and compliance Omega-6 hormones amplify insults into inflamed injuries Omega-3 HUFA diminish inflammatory insults Known diet-tissue relationship to predict food impacts No prescription needed to: TO TEACH - Computer-aided food choice to counsel good food combinations EAT FEWER CALORIES PER MEAL EAT LESS OMEGA-6 EAT MORE OMEGA-3

20 FOOD amino acids nucleosides acetyl-coa fatty acids sugars HMG-CoA essential FA statin mevalonate Biomarker % n-6 in HUFA of tissue phospholipids n-3 & n-6 HUFA release aspirin XS n-6 hormones platelet activation isoprenoids prenylated proteins vessel wall plaques ischemia thrombosis arrhythmia malonyl-coa squalene Connecting primary cause to consequences cholesterol oxidant stress & inflammation & proliferation & impaired NO CO 2 O 2 Fatty acyl-coa Biomarkers VLDL Triglyceridemia Morbidity & Mortality + electrons ADP work H 2 O exercise ATP synthesize Obesity & BMI FFA + LDLcholesterol Insulin resistance Elevated glucose Excess food energy causes transient insults with every meal Also CRP ENHANCE ACCORD ADVANCE VA-Diabetes Jupiter Clinical trials using indirect biomarkers

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22 American College of Nutrition 52 nd Meeting, Nov.19, 2011 Clinical Nutrition as Core Medicine 1.- Defining and Filling Practice Gaps (esp. data transfer and attitudes) - Recognize selective eicosanoid receptors are in nearly every cell and tissue - Know the chain of events connecting vitamin>>hormone>>disease - Raise priority of causal mediators over mere associated/predictive risk factors - Know more of current %n-6 in HUFA status and preventable healthcare costs - Prevent the cause of signs do not just suppress signs and symptoms - Discuss preventable financial losses with patients, families and CEOs - Implement primary prevention -Stop silo mentality that prevents constructive feedback of information 2.- Encourage new tools to monitor and manage causal mediators of wellness - Faster, cheaper, high-throughput assays of HUFA proportions in individuals - Simple apps for informed decisions on foods, supplements & nutraceuticals

23 Continuing preventable disease - is a paradox due to neglected information and imprecise terms Good medical practice will - - Remove a preventable cause of disease not just a sign or symptom produced by the cause - - Use biomarkers that monitor causal connections - - Know that NOT all predictive risk factors cause disease and we should not over-interpret associations! - - Know explicit contexts for terms being used. Paradoxes in current advice to the public Lands, Prog.Lipid Res. 2008; 47: