Omega3 Fatty Acids and Inflammation

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Omega-3 Fatty Acids and Inflammation

• Laura Jacob
• FCS 5152
• Readings in Nutrition Research

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Inflammation Associated Conditions

• Many studies
• CVD
• Arthritis

• A few studies
• Asthma
• Lung Disease
• IBD
• Atopic Eczema
• Alzheimers disease
• Cancer
• Trauma/Surgery

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Preview of presentation

• Background study
• Inflammatory process
• Review of fatty acids
• Role of omega-3 in inflammation

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Preview, continued

• CVD studies
• Arthritis studies
• Sources of omega-3
• Summary conclusions
• Implications practical applications for
  dietetics professionals

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Where it began

• Epidemiological and prospective studies led to
  awareness of fatty acids roles in inflammation
• Began with study of Eskimos
• High meat diet
• Very low incidence of CVD

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Bang, Dyerberg, Nielsen

• 1971
• Greenland Eskimos
• 130 Eskimo subjects
• (hunters or fishermen)
• Danish controls
• Examined lipid profiles
• Bang HO, Dyerberg J, Nielsen A. Plasma lipid
  and lipoprotein pattern in Greenlandic west-coast
  Eskimos. Lancet. 1971June 51143-1145.

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Bang, Dyerberg, Nielsen, cont.

• 1971 Greenland Eskimo diet
• Meat of whales, seals, sea birds
• Fish halibut, capelin, salmon
• High in polyunsaturated fat

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Purpose

• To examine the effectiveness of omega-3 fatty
  acids in prevention and treatment of conditions
  associated with inflammation

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The Inflammatory Process

• Response to infection or injury
• Natural part of immune response
• Calder PC. Fatty acids and gene expression
  related to inflammation. In Clinical Nutrition
  Early Intervention. 2001 19-25.

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Bad Inflammation

• Uncontrolled
• Inappropriate
• Excessive

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Essential Fatty Acid Review

• Omega-6
• Linoleic acid (LA) 182n-6
• Arachidonic acid (AA) 204n-6
• Omega-3
• Linolenic acid (ALA) 183n-3
• Eicosapentaenoic acid (EPA) 205n-3
• Docosahexaenoic acid (DHA) 226n-3
• Wildman REC, Medeiros DM. Advanced Human
  Nutrition. P. 101

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Inflammatory Mediator Precursors

• Arachidonic acid
• Omega-6 fatty acid
• From diet, or from linoleic acid
• EPA and DHA
• Omega-3 fatty acids
• From diet, or from linolenic acid

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Metabolism of n-3 n-6

• Omega-3
• a-Linolenic acid
• Eicosapentaenoic acid
• Docosahexaenoic acid

• Omega-6
• Linoleic acid
• Arachidonic acid

Competition
Adapted from Clinical Nutrition Early
Intervention, p.22, fig. 2
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AA vs. EPA DHA

• AA in cell membrane phospolipids
• Free AA
• PG2, TX2, LT4
• Inflammation

• EPA DHA in cell membrane phospolipids
• Free EPA
• PG3, TX 3, LT5
• Less Inflammation

LOX COX
Adapted from Clinical Nutrition Early
Intervention. 2002. p. 24, fig. 4
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Prostaglandins,Leukotrienes, Thromboxanes

• Eicosanoid hormones
• Regulate intensity and duration of response
• Arachidonic acid products
• PGE2, TX2, LTB4 TNF, IL-1, IL-6
• EPA and DHA products
• PG3, TX3, LT5

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• Arachidonic acid
• PGE2, TX2, LTB4
• TNF, IL-1, IL-6
• Promote
• Inflammation

• EPA and DHA
• PG3, TX3, LT5
• Oppose
• Inflammation

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• Questions?

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CVD Studies

• GISSI-Prevenzione Trial
• Physicians Health Study
• Lyon Diet Heart Study

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GISSI-Prevenzione

• A mortality study
• Examined n-3 vitamin E supplements on risk of
  death
• 11,324 subjects
• Recent MI lt or 3 months prior
• Endpoints death, non-fatal MI, stroke
• GISSI-Prevenzione Investigators. Dietary
  supplementation with n-3 polyunsaturated fatty
  acids and vitamin E after myocardial infarction
  results of the GISSI-Prevenzione trial. Lancet.
  1999354447-455.

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GISSI-Prevenzione

• Subjects randomly assigned
• Treatments
• n-3 (1 g)
• Vitamin E (300 mg)
• Both
• None (control group)
• Follow-up visits
• Months 6, 12, 18, 30, 42
• Food frequency questionnaire

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Hypothesis

• The combined n-3 vitamin E treatment would
  decrease the rate of death, non-fatal MI, and
  non-fatal stroke by 20 over n-3 or vitamin E
  alone.

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Results

• Diet, prevention treatments, and
  revascularization procedures well-balanced across
  groups
• Treatment with omega-3 PUFA was beneficial for
  main endpoints

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Percent Decrease in risk of Individual Endpoint
Components

• All fatal events 20
• CV death 30
• Cardiac death 35
• Coronary death 35
• Sudden death 45
• Fatal non-fatal stroke 30 Increase

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Physicians Health StudyAlbert, et. al.

• Prospective case-control analysis
• Part of Physicians Health Study
• Hypothesis the long-chain n-3 fatty acids found
  in fish are associated with a reduced risk of
  sudden death from cardiac causes in those without
  known cardiovascular disease.

Albert, et.al. Blood levels of long-chain n-3
fatty acids and the risk of sudden death. N Engl
J Med. 20023461113-1118.
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Participants Treatment

• Out of 22,071 male physicians
• 94 subjects
• 184 controls
• Aged 40-84 in 1982
• No history of MI, stroke, TIA, or cancer

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Methods

• Health status questionnaires completed
• Food frequency questionnaire
• CV event info collected
• Base-line blood samples were collected
• Endpoint sudden cardiac death

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Results

• Inverse relationship between blood omega-3 and
  risk of sudden death
• Lowest risk with highest levels

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Adapted from Albert, et. al. Blood levels of
long-chain n-3 fatty acids and the risk of sudden
death. 200234611131118.
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Lyon Diet Heart Studyde Lorgeril et. al.

• A prosective, randomized, single-blinded clinical
  trial aimed at prevention of MI recurrence
• Diet modification
• Subjects
• lt 70 years old
• Survived recent MI

de Lorgeril, et.al. Mediterranean
alpha-linolenic acid-rich diet in secondary
prevention of coronary heart disease. Lancet.
19943431454-1460.
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Lyon Diet Heart Study, cont.

• Dietary intervention Experimental group
• More bread, more root and green veg, more fish,
  less meat, fruit daily
• Butter and cream replaced with study supplied
  margarine (high in ALA)
• Canola and olive oil for salads and cooking
• Diet Control group
• Traditional advice from physicians

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Results

• 76 reduction in risk of cardiac death
• Similar between groups
• TC, TG, lipoproteins, weight, BP

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ALA vs. EPA DHAFreese Mutanen

• Compared effects of ALA to EPA DHA on
  hemostatic factors
• Blind, parallel supplementation trial
• 46 healthy subjects completed study
• 3 phases pre-experimental, experimental (4
  wks), follow-up (12 wks)

Freese Mutanen. Alpha-linolenic acid and
marine long-chain n-3 fatty acids differ only
slightly in their effects on hemostatic factors
in healthy subjects. Am J Clin Nutr.
199766591-598.
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Freese Mutanen, cont.

• ALA group (flaxseed oil)
• 55 linolenic, 15 linoleic supplement
• EPA DHA group (fish oil)
• EPA 33, DHA 27
• Blood samples collected

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Results

• Benefits did not differ between groups for
  hemostatic factors
• Collagen-induced platelet aggregation
• Thromboxane production
• Bleeding time
• Plasma fibrinogen concentration
• Antithrombin III activity
• Factor VII coagulant activity
• Plasminogen activator inhibitor activity

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Results, cont.

• Positive effects in fish oil group not seen in
  flaxseed oil group
• Decreased triglycerides
• Decreased total cholesterol
• Conclusion flaxseed oil fish oil
  supplementation both lead to positive hemostatic
  changes. Only fish oil leads to decreased TC and
  TG.

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Rheumatoid Arthritis

• A chronic autoimmune disease
• Inflammation of joints (often the hands)
• Persistent inflammation may lead to
• Cartilage destruction
• Bony erosions
• Progressive disability
• NCHS 20 of non-institutionalized adults have
  symptoms

Tidow-Kebritchi S Mobarhan S. Effects of diets
containing fish oil and vitamin E on rheumatoid
arthritis. Nutrition Reviews. 200159335-341.
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Rheumatoid Arthritis, cont.

• Responsible substances
• Cytokines, activated lymphocytes, macrophages,
  fibroblasts
• Esp. IL-1, IL-6, and TNF-alpha

Tidow-Kebritchi S Mobarhan S. Effects of diets
containing fish oil and vitamin E on rheumatoid
arthritis. Nutrition Reviews. 200159335-341.
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Thies, et.al.

• Randomized, placebo-controlled, double-blind,
  parallel study
• Purpose to determine the effect of dietary
  supplementation with ALA, GLA, AA, DHA, or fish
  oil on the proliferation of mononuclear cells and
  on the production of cytokines by those cells.

Thies F, et. al. Dietary supplementation with
gamma-linolenic acid or fish oil decreases T
lymphocyte proliferation in healthy older humans.
J Nutr. 20011311918-27.
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Thies, et.al., cont.

• 55 healthy subjects, 55-75 years old
• 6 groups
• 2 g ALA
• 770 mg GLA
• 680 mg AA
• 720 mg DHA
• 1 g EPA and DHA (Fish oil)
• Placebo

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Results

• All supplements increased their proportion in
  phospholipids, esp. fish oil
• Number proportion of lymphocytes did not differ
  among groups
• Fish oil GLA decreased lymphocyte proliferation

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Arthritis Studies

• Review Joel Kremer
• Reduction in tender joints 6 studies
• Reduction in morning stiffness- 3 studies
• Both findings confirmed in meta-analysis
• Reduction in NSAID use

Kremer JM. N-3 fatty acid supplements in
rheumatoid arthritis. Am J Clin Nutr.
200071349S-351S.
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Good Sources of Omega-3

• EPA DHA
• Fish (esp. fatty) and seafood
• ALA
• Vegetable oil best source
• Nuts, seeds, vegetables

Kris-Etherton, et.al. Polyunsaturated fatty
acids in the food chain in the US. Am J Clin
Nutr. 200071179S-188S.
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Fatty Acid Content of Seafoods-Grams/100 g
edible portion

• Mackerel 1.8 - 5.3g
• Herring 1.2 - 3.1g
• Salmon 1.0 1.4g
• Tuna 0.5 1.6g

Adapted from Kris-Etherton et al.
Polyunsaturated fatty acids in the food chain in
the US. Am J Clin Nutr. 200071180S.
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Adapted from Wildman Medeiros. Advanced Human
Nutrition, 2000, and Morris. Essential Nutrients
other functional compounds in flaxseed.
Nutrition Today, 2001.
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Other Vegetable SourcesGrams/100 g edible portion

• Flaxseed 22.8g
• Walnuts 3.3 6.8g
• Soybeans (roasted) 1.5g
• Soybeans (raw) 3.2g
• Purslane (also contains EPA) 0.4 g
• Oats (germ) 1.4g
• Seaweed (spirulina) 0.8g

Adapted from Kris-Etherton et al.
Polyunsaturated fatty acids in the food chain in
the US. Am J Clin Nutr. 200071180S.
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Summary

• Omega-3 fatty acids have positive benefits
• EPA has greatest benefits
• Side effects
• ALA beneficial
• Need more research
• Good idea for healthy people

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Applications

• AI for men
• 17 g linoleic acid
• 1.6 g alpha-linolenic acid
• AI for women
• 12 g linoleic acid
• 1.1 g alpha-linolenic acid
• AHA
• Healthy people-2 fish meals/wk
• CHD- 1 g EPA/DHA per day

Source Dietary Reference Intakes, 2002. U.S.
Food and Nutrition Board