Effects of Seal Oil Supplementation on Risk Factors

for Cardiovascular Disease in Human Subjects

Conference on Seal Oil, Collagen, and Protein ProductsJune 7-8th, 2004 - DFAIT, Ottawa

Professor Bruce J. HolubDepartment of Human Biology and Nutritional Sciences

University of GuelphGuelph, ON Canada N1G 2W1

bholub@uoguelph.ca

Fatty Acid Composition of Encapsulated Seal Oil

Fatty Acids Seal Oil (% of total)

ΣSats 11.9

ΣMono 58.516:1n-7 16.718:1n-9 25.520:1n-11 11.8

ΣPUFA 29.6n-6 3.4n-3 26.220:5 (EPA) 8.322:5 (DPA) 4.922:6 (DHA) 10.4

DPADocosapentaenoic Acid

22:5 n-3

Rationale for Research/Health Interest in Dietary Docosapentaenoic Acid (DPA, 22:5n-3)

1.) Is a substantial component of the Greenland Inuit diet rich in marine mammals (Bang et al., AJCN, 33:2657-2661, 1980) and diet of Inuit in northern Quebec.

2.) Fish oils enriched in EPA/DHA (low DPA) and seal oils contain EPA/DHA plus significant levels of DPA.

3.) DPA levels in serum phospholipid have been inversely correlated with coronary heart disease risk (Simon et al., Am. J. Epid., 142:469-476, 1995).

4.) Might DPA offer any potential benefits with respect to CVD/cardioprotection?

Principle Meat/Fish Consumed by Selected Households in Qeqertarsuaq, 1989-1990 (source: field data)

Polar Bear1%

Fish24%

Seal/Walrus20%

Other4%

Minke Whale6%

Birds 12%

Lamb 3%

Imported Foods 16%Beluga/Narwhal 7%

Caribou 7%

The Fatty Acid Comparisons of Serum Phospholipids of Postmenopausal Women

From Greenland and Canada

Stark KD, Mulvad G, Pedersen HS, Park EJ, Dewailly E, and Holub BJ.

University of Guelph, Guelph, ON, CanadaCenter of Primary Health Care, Nuuk, Greenland

Laval University, QC, Canada

Comparison of n-3 Fatty Acid Compositions of Serum Phospholipid in Postmenopausal

Women (mean ± SEM)

Ref: Stark et al., Nutrition, 18: 627-630, 2002.

0

1

2

3

4

5

6

7

8

9

Canada

Greenland

*

*

*

EPA (20:5n-3) DHA (22:6n-3) DPA (22:5n-3)

Epidemiological/Population Studies

1.) Higher levels of docosahexaenoic acid (DHA, 22:6 n-3) and docosapentaenoic acid (DPA, 22:5 n-3) in serum phospholipid have been associated with decreased coronary heart disease risk.(Simon et al., Am. J. Epidemiol., 142: 469-476, 1995.)

2.) Higher levels of eicosapentaenoic acid (EPA, 20:5 n-3) and docosapentaenoic acid (DPA, 22:5 n-3) in platelet phospholipid have been associated with reduced coronary artery disease (Hodgson et al., AJCN, 58:228-234, 1993).

Ref: Rissanen et al., Circulation, 102: 2677-2679, 2000.

Relative Risk of Acute Coronary Events in Relation to Serum DHA and DPA Levels

DHA + EPA as % of total serum fatty acids

<2.38 2.38-2.73 2.74-3.07 3.08-3.58 >3.58

Rel

ativ

e R

isk

(RR

)

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

Dietary Vegetable Oils As Source of Omega-3

α-Linolenic Acid 18:3n-3 (Canola, Flaxseed, Soybean)

18:4n-3

20:4n-3

20:5n-3

22:5n-3

22:6n-3

Desaturation

Elongation

Desaturation

Elongation

Desaturation

Dietary Fish/Fish Oil(EPA/DHA)

(EPA)

(DHA)

0

50

100

150

% o

f day

0 le

vels

Omega-3 Levels in Total Human Platelet Phospholipid (after flax rich in α-LNA)

20:5n-3EPA

22:5n-3DPA

22:6n-3DHA

**

Effects of Dietary Consumption of Omega-3 Fatty Acids on Physiological DPA (22:5n-3) Status*

Dietary Fatty Acids/Oils DPA Status

1) α–LNA (flax, canola)

2) EPA + DHA (fish oils)

3) EPA alone

4) DHA alone

5) EPA + DHA + DPA (seal oil)

*Based on DPA (22:5n-3) levels in human serum/platelet phospholipid.

Common Dietary Sources (N. Am.) of DPA (22:5 n-3) in Cellular Phospholipid

1.) α–LNA (18:3 n-3): via desaturation/elongation (approx. 150mg/day of DPA generated per 1.5g α-LNA/diet)

2.) EPA (20:5 n-3): via elongation (<50mg/day of DPA generated)

3.) DPA (22:5n-3): direct consumption (approx. 18mg/day in N. Am. and approx. 1,000-3,000 mg/day in Greenland Inuit)

4.) DHA (22:6n-3): via retroconversion (<50mg/day of DPA generated)

Effects of Supplementation with Dietary Seal Oil on Selected

Cardiovascular Risk Factors And Hemostatic Variables in Healthy

Male Subjects

Conquer J, Cheryk L, Chan E, Gentry P, & Holub B.University of Guelph

Subjects: 20 healthy males (29.5 ± 1.5 yr)

Supplement: 20 g/day of encapsulated plant oil (placebo) or seal oil (providing 0.8g DPA plus 1.3 g EPA plus 1.7 g DHA/day)

Duration: 42 days with blood sampling and analysis at days 0, 21, and 42.

Experimental Design

0

1

2

3

4

5

6

7%

of

fatt

y ac

ids

in s

erum

PL EPA

DPA

DHA

*

**

*

* *

0 21 42Day

0 21 42 0 21 42

DayDay

( by 7%)

( by 19%)

Seal Oil

*

Placebo (Oil)

Fib

rinog

en (

g/L)

Pro

tein

C (

u/m

L)*

0 42 0 42Days

0

0.5

1.0

1.5

2.0

2.5

0

0.2

0.4

0.6

0.8

(EPA+DHA) as % of Fatty Acids in Plasma Phospholipid

Rel

ativ

e R

isk

(IH

D/M

I)

0

0.5

1.0

(Ref. Lemaitre et al., Am J Clin Nutr, 77:319, 2003)

3 6

non-fatal MI

(one SD above mean)

FatalIschemic

Heart Disease

(one SD above mean)70% lower

(EPA + DHA) Levels and Risk of Fatal Ischemic Heart Disease

CHD Risk

(desirable)

High Medium Low

0.0 3.6 4.6 12

(EPA + DHA as % of fatty acids in serum phospholipid)

Ref: Based on Lemaitre et al., Am. J. Clin. Nutr., 77:319 (2003).

3.47Before

11.0After

Docosahexaenoic acid and docosapentaenoic acid

incorporated into human platelets after 24 and 72 hours: Inhibitory

effects on platelet reactivity

L.A. Cheryk, J.A. Conquer, B.J. Holub, P.A. GentryUniversity of Guelph, Guelph, Ontario, Canada

Ref: Platelet, 10: 203-211, 1999.

Effect of DPA (22:5n-3) Addition (at 200 uM) on Thromboxane B2 Generation and Collagen-

Induced Human Platelet Aggregation

%age of Controls

Incubation time TxB2 release % Max. Aggregation

24 hours 56 18

72 hours 41 0