omega-3 fatty acids in critical illness: mechanisms and clinical ... · lists fatty acids in foods...

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.

Clinical Effects Incorporation & Washout

Balance in the Tissue is the Issue

BS vanderMeij et al, Am.J.Clin.Nutr. 2011; 94: 1248-1265

Found = 2921 Enteral Parenteral

1146 1775

“Potential” studies 93 98

RCTs included 14 14

Found = 5111 Enteral Parenteral

2309 2802

“Potential” studies 171 72

Studies included 27 9

Concluded beneficial effects of n-3FA supplementation

See also meta-analysis of parachutes:

GCS Smith and JP Pell, Brit Med J. 2003; 327: 1459

Know Your Numbers

OPTIMAL NUTRITION STATUS means:

much chronic disease prevented

many treatments not needed

Know Their Context

1. Your food’s Omega-3 Balance Scores

2. Your blood’s %omega 3 in HUFA

3. Your annual healthcare claim costs

USDA Nutrient Database

lists fatty acids in foods

Finger-tip blood-spot assay

lists fatty acids in blood

Use 11 n-3 & n-6 acids

to form one value of

Omega-3 Balance Score

Use 8 n-3 & n-6 HUFA

to form one value of

%Omega-3 in HUFA

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)

Chicken

- 7.8

Coho salmon

+52.6

Pork

- 4.3

Turkey

- 10.9

Omega-3 Balance Scores

Beef steak

- 2.0

Crab

+ 30.6

http://www.fastlearner.org/Omega-3Balance.htm

Highly Unsaturated Fatty Acids (HUFA)

have 20- and 22-carbons & 3 or more double bonds

Linolenic acid (18:3n-3) ALA Linoleic acid (18:2n-6) LA

OMEGA-3 OMEGA-6

Eicosapentaenoic (20:5n-3)EPA Arachidonic acid (20:4n-6) AA

Docosahexaenoic (22:6n-3) DHA DPA (22:5n-6)

Dihomoγlinolenate (20:3n-6) DGLA

DPA (22:5n-3) Adrenic Acid (22:4n-6)

From Vitamins to Hormones: Competition is the Context

Stearidonic acid (18:4n-3) Gamma-linolenic acid (18:3n-6)

HUFA make hormones

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 =

$5,184

$10,000

employee 10 thousand

employees

$51,840,000

>millions

$2,250,000,000,000

>trillions $15,200

150 million

employees

$152,000,000

>millions

$777,000,000,000

>billions

If we can prevent half of this, why don’t we?

When disease is prevented, treatment costs are not needed

FOOD

amino acids

nucleosides

fatty acids

sugars

essential FA

oxidant stress &

inflammation &

proliferation &

impaired nitric oxide

% n-6 in HUFA of

tissue phospholipids

n-3 & n-6 HUFA release

XS n-6 eicosanoids

vessel wall

plaques

thrombosis

ischemia

arrhythmia

Morbidity &

Mortality

platelet activation

aspirin

Biomarker <<This is a valid surrogate endpoint for nutrition-based

primary prevention of CHD morbidity & mortality

Connecting the primary cause

to its consequences

arthritis

asthma

colon cancer

length of hospital stay

psychiatric disorders

workplace disruption

health care $$ claims

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

Wada et al., J Biol Chem. 2007; 282(31):: 22254-66.

Relative n-3 & n-6

actions with

enzymes & receptors

Overall,

n-3 forms act

less intensely

than n-6 forms.

Release HUFA

Oxidize HUFA

to intermediates

Make hormones

Hormone

receptor

actions

Tissue HUFA Eicosanoids

Differ

3

Anything 3 can

do

I can do better!

Good grief!

Sometimes 6 is just too

much!

6

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

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

CH

D M

ort

ality

Greenland

Japan

Quebec Inuit

Quebec Cree

USA

Quebec Urban

When disease is prevented, treatment costs are not needed.

Americans have high omega-6 in HUFA & an omega-3 deficit

Heart

Att

ack D

eath

Rate

% omega-6 in HUFA

= MRFIT

quintiles

Relative risk - -

Siscovick,1995

&

Alberts, 2002

$2,076/yr

$3,930/yr

$3,052/yr

WV-PEIA=$6,408

Health Claim Cost

USA=$5,184/yr

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.

location %HUFA %6inH

Detroit - 2009 19 78

Baltimore-2008 24 79

Quebecer-2001 8 78

ARIC study-2007 15 77

Detroit-2005 12 82

Columbus, 2007 13 87

avg. = 15 80

location %HUFA %6inH

Detroit - 2009 19 78

Baltimore-2008 24 79

Quebecer-2001 8 78

ARIC study-2007 15 77

Detroit-2005 12 82

Columbus, 2007 13 87

avg. = 15 80

+3 +2 +1 0 -1 -2 -3 -4 -5 -6 -7 -8

Related %omega6 in HUFA


Diverse Food Habits and Tissue Consequences

72% 67% 62% 57% 52% 47% 42% 37% 32% 27% 22% 17% 12%

28% 33% 38% 43% 48% 53% 58% 63% 68% 73% 78% 83% 88%

Average daily menu balance


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

We started with lots of -7 values - - - We changed to lots of -3

http://www.fastlearner.org/pdfs/Eat3.pdf

http://www.fastlearner.org/pdfs/Nix6.pdf

Chicken

- 7.8

Coho salmon

+52.6

Pork

- 4.3

Turkey

- 10.9

Omega-3 Balance Scores

Beef steak

- 2.0

Crab

+ 30.6


Wheat

- 1.6

Corn

- 2.6

Rice

- 0.4

Oatmeal

- 5.5

Barley

- 1.5

Quinoa

- 5.6

Rye

- 1.1

Buckwheat

- 1.7

Kellog’s Corn Flakes

- 1.0

Flax meal

+ 28.1


+3 +2 +1 0 -1 -2 -3 -4 -5 -6 -7 -8


Diverse Food Habits and Tissue Consequences

28% 33% 38% 43% 48% 53% 58% 63% 68% 73% 78% 83% 88%

Average daily menu balance


Parenteral Foods and Their Balance Scores

Omegaven (10%) + 49 Lipoven (10%) - 9

Lipoplus (20%) + 7 Intralipid (20%) - 20

Tools for Primary Prevention

Low-cost assay of %n-6 in HUFA

to monitor risk and compliance

Known diet-tissue relationship

to predict food impacts

Computer-aided food choice

to counsel good food combinations

Effective Primary Prevention Needs You

TO UNDERSTAND–

Food energy causes transient tissue insults

Omega-6 hormones amplify insults into inflamed injuries

Omega-3 HUFA diminish inflammatory insults

TO TEACH -

EAT FEWER CALORIES PER MEAL

EAT LESS OMEGA-6

EAT MORE OMEGA-3

When disease is prevented,

treatment costs are not needed

No prescription needed to:

Clinical trials using

indirect biomarkersConnecting primary cause

to consequences

ACCORD

ADVANCE

VA-Diabetes

ENHANCE

Also CRP

FOOD

amino acids

nucleosides

fatty acids

sugars

essential FA

acetyl-CoA malonyl-CoA

Fatty acyl-CoA

VLDL

HMG-CoA

mevalonate

isoprenoids

prenylated proteins

cholesterol

oxidant stress &

inflammation &

proliferation &

impaired NO

FFA + LDLcholesterol

Triglyceridemia

Obesity

Insulin resistance

Elevated glucose

vessel wall

plaques

thrombosis

ischemia

arrhythmia

Morbidity &

Mortality

platelet activation

statinBiomarkers

Excess food energy

causes transient insults

with every meal

squalene

% n-6 in HUFA of



XS n-6 hormones

aspirin

Biomarker

FOOD

amino acids

nucleosides

fatty acids

sugars

essential FA

acetyl-CoA malonyl-CoA

Fatty acyl-CoA

VLDL

HMG-CoA

mevalonate

isoprenoids

prenylated proteins

cholesterol

oxidant stress &

inflammation &

proliferation &

impaired NO

FFA + LDLcholesterol

Triglyceridemia

Obesity

Insulin resistance

Elevated glucose

vessel wall

plaques

thrombosis

ischemia

arrhythmia

Morbidity &

Mortality

platelet activation

statinBiomarkers

Excess food energy

causes transient insults

with every meal

squalene

% n-6 in HUFA of



XS n-6 hormones

aspirin

Biomarker

Jupiter

CO2 O2

+ electrons ADP work

H2O exercise

ATP synthesize

CO2 O2

+ electrons ADP work

H2O exercise

ATP synthesize

& BMI

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

American College of Nutrition – 52nd Meeting, Nov.19, 2011

“Clinical Nutrition as Core Medicine”

Paradoxes in current advice to the public

Lands, Prog.Lipid Res. 2008; 47: 77-106.

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.

“Continuing preventable disease” - is a paradox

due to neglected information and imprecise terms

omega-3 fatty acids in critical illness: mechanisms and clinical ... · lists fatty acids in foods...

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