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.
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.
Balance in the Tissue is the Issue Incorporation & Washout Found = 5111 Enteral Parenteral 2309 2802 Potential studies 171 72 Studies included 27 9 Clinical Effects Found = 2921 Enteral Parenteral 1146 1775 Potential studies 93 98 RCTs included 14 14 Concluded beneficial effects of n-3fa supplementation BS vandermeij et al, Am.J.Clin.Nutr. 2011; 94: 1248-1265 See also meta-analysis of parachutes: GCS Smith and JP Pell, Brit Med J. 2003; 327: 1459
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
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 14:0 1.30 0.20 Myristic 14:0 1.30 0.20 Myristic 14:1 1.59 0.05 Myristoleic 14:1 1.59 0.05 Myristoleic 15:0 2.37 0.18 Pentadecanoic 15:0 2.37 0.18 Pentadecanoic 15:1 0.34 0.09 15:1 0.34 0.09 16:0 23.41 21.05 Palmitic 16:0 23.41 21.05 Palmitic 16:1w5 0.00 0.08 16:1w5 0.00 0.08 16:1w7 2.30 0.70 Palmitoleic 16:1w7 2.30 0.70 Palmitoleic 17:0 0.00 0.21 Heptadecanoic 17:0 0.00 0.21 Heptadecanoic 17:1 0.00 0.62 17:1 0.00 0.62 18:0 9.05 12.53 Stearic 18:0 9.05 12.53 Stearic 18:1w9 17.96 8.87 Oleic 18:1w9 17.96 8.87 Oleic 18:1w7 0.00 2.24 Vaccenic 18:1w7 0.00 2.24 Vaccenic 18:1w5 0.00 0.35 18:1w5 0.00 0.35 18:2w6 27.08 23.90 Linoleic (LA) 18:2w6 27.08 23.90 Linoleic (LA) 18:3w6 0.32 0.12 gamma-linolenic (GLA) 18:3w6 0.32 0.12 gamma-linolenic (GLA) 18:3w3 0.74 0.21 alpha-linolenic (ALA) 18:3w3 0.74 0.21 alpha-linolenic (ALA) 18:4w3 0.00 0.10 Stearidonic (SDA) 18:4w3 0.00 0.10 Stearidonic (SDA) 20:0 0.00 0.33 Arachidic 20:0 0.00 0.33 Arachidic 20:1w9 0.00 0.04 20:1w9 0.00 0.04 20:1w7 0.00 0.22 20:1w7 0.00 0.22 20:2w6 0.60 0.47 Eicosadienoic 20:2w6 0.60 0.47 Eicosadienoic 20:3w9 0.31 0.13 Mead's acid 20:3w9 0.31 0.13 Mead's acid 20:3w6 1.55 3.41 Dihomogammalinolenic (DGLA) 20:3w6 1.55 3.41 Dihomogammalinolenic (DGLA) 20:4w6 6.43 12.81 Arachidonic (AA) 20:4w6 6.43 12.81 Arachidonic (AA) 20:3w3 0.00 0.07 Eicosatrienoic (n-3) 20:3w3 0.00 0.07 Eicosatrienoic (n-3) 20:4w3 0.00 0.04 Eicosatetraenoic (n-3) 20:4w3 0.00 0.04 Eicosatetraenoic (n-3) 20:5w3 0.36 0.59 Eicosapentaenoic (EPA) 20:5w3 0.36 0.59 Eicosapentaenoic (EPA) 22:0 0.62 1.11 Behenic 22:0 0.62 1.11 Behenic 22:1w9 0.34 0.01 Erucic 22:1w9 0.34 0.01 Erucic 22:4w6 0.97 0.76 Docosatetraenoic 22:4w6 0.97 0.76 Docosatetraenoic 22:5w6 0.66 0.60 Docosapentaenoic (n-6) 22:5w6 0.66 0.60 Docosapentaenoic (n-6) 22:5w3 0.44 1.13 Docosapentaenoic (n-3) 22:5w3 0.44 1.13 Docosapentaenoic (n-3) 24:0 0.00 0.88 Lignoceric 24:0 0.00 0.88 Lignoceric 22:6w3 1.03 3.59 Docosahexaenoic (DHA) 22:6w3 1.03 3.59 Docosahexaenoic (DHA) Use 8 n-3 & n-6 HUFA to form one value of %Omega-3 in HUFA
Omega-3 Balance Scores http://www.fastlearner.org/omega-3balance.htm Coho salmon +52.6 Beef steak - 2.0 Crab + 30.6 Pork - 4.3 Chicken - 7.8 Turkey - 10.9
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
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 $15,200 10 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?
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
Eicosanoids Wada et al., J Biol Chem. 2007; 282(31):: 22254-66. 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 http://efaeducation.nih.gov/sig/beginners.html
Heart CHD Attack Mortality Death Rate Americans have high omega-6 in HUFA & an omega-3 deficit 200 150 100 CHD Mortality and Tissue HUFA y = 3.0323x - 74.8 R 2 = 0.9866 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 20 30 40 50 60 70 80 % 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.
location location %HUFA %HUFA %6inH %6inH troit - 2009 Detroit - 2009 19 19 78 78 ltimore-2008 Baltimore-200824 24 79 79 ebecer-2001 Quebecer-20018 878 78 IC study-2007 ARIC study-2007 15 15 77 77 troit-2005 Detroit-2005 12 12 82 82 lumbus, Columbus, 2007 2007 13 13 87 87 avg. = avg. 15= 15 80 80 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.
Diverse Food Habits and Tissue Consequences Average daily menu balance +3 +2 +1 0-1 -2-3 -4-5 -6-7 -8 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% http://www.fastlearner.org/omega-3balance.htm
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
http://www.fastlearner.org/pdfs/nix6.pdf http://www.fastlearner.org/pdfs/eat3.pdf
Omega-3 Balance Scores http://www.fastlearner.org/omega-3balance.htm Coho salmon +52.6 Beef steak - 2.0 Crab + 30.6 Pork - 4.3 Chicken - 7.8 Turkey - 10.9
Rye - 1.1 Rice - 0.4 Barley - 1.5 Wheat - 1.6 Kellog s Corn Flakes - 1.0 Corn - 2.6 Buckwheat - 1.7 Oatmeal - 5.5 Flax meal + 28.1 Quinoa - 5.6 http://www.fastlearner.org/omega-3balance.htm
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 +3 +2 +1 0-1 -2-3 -4-5 -6-7 -8 http://www.fastlearner.org/omega-3balance.htm Related %omega6 in HUFA 28% 33% 38% 43% 48% 53% 58% 63% 68% 73% 78% 83% 88%
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
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
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
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: 77-106.