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University of Tromsø – Faculty of Medicine uit.no

Can seal oil contribute to better human health?

Bjarne Østerud and Edel O. Elvevoll, Faculty of Medicine and NFH,

University of Tromsø

E-mail: bjarne@fagmed.uit.no

(2)

University of Tromsø – Faculty of Medicine uit.no

Historical background

• Old food lore of seafood

• It makes you smart

• It makes you stay healthy

• Has obtained some support in science

• Dietary habits have changed

• Last 200 years

• Relative total fat,

saturated fat and n-6 increased

• Relative n-3 decreased

• Incidents of CHD increased

Saturated Fat Coronary Heart

Disease

Calories from fat, %

Year

4 0 5 0

2 0 3 0

1 0

0

10,00 0 BC

180 0

195 0 190

0

200 0

Total Fat

4 mil.

BC

n- 6 n-3

185 0

(3)

University of Tromsø – Faculty of Medicine uit.no

Greenland Eskimos, on their

traditional diet - lower incidence of CHD

( Dyerberg et al., 1978)

Omega-3 protects against atherosclerosis and thrombosis

• Marine mammals and Fish

• Visceral organs (liver, kidney, heart)

• Raw or minimal processed food

(4)

University of Tromsø – Faculty of Medicine

Functional “molecules” from seafood

n-3 (omega-3) Fatty Acids:

eicosapentaenoic (EPA, 20:5), docosahexenoic acid (DHA, 22:6)

Peptides/ Proteins:

Fish protein hydrolysates

Angiotensin converting enzyme (ACE) inhibitors Serine protease inhibitors

Amino acids:

taurine, lysine, histidine, glutamine

Vitamins: A, D, E and K ...Ubiquinone CoQ10….niacin, B6, B12

Minerals and trace elements:

potassium, calcium, magnesium, zinc, selenium, iodine

..be aware of the risk of overfocusing single aspects..

(5)

University of Tromsø – Faculty of Medicine uit.no

Different types of cholesterol

-HDL-cholesterol: the good cholesterol -LDL-cholesterol: the bad cholesterol

Therefore we want to increase HDL-cholesterol and reduce LDL-cholesterol

HDL-cholesterol is enhanced by:

-Physical exercise

-Alcohol (red wine is recommended)

-Omega-3 fatty acids (specially in seal-and whale oil

LDL-cholesterol is reduced by:

-Intake of fish

-Less intake of saturated fatty acids (bacon, lamb, etc)

-More intake of white meat -Increased intake of vegetables

(6)

University of Tromsø – Faculty of Medicine

Intake of food that contains cholesterol may be beneficial:

Those who don’t have inherited

hypercholesterolemi can eat egg and other products which contains cholesterol with a positive effect

Why? The cholesterol in the diet will

reduce the production of cholesterol in the

liver!

(7)

University of Tromsø – Faculty of Medicine uit.no

Mechanism of atherogenesis

-a short review

(8)

University of Tromsø – Faculty of Medicine

Atherogenesis

Arterial wall

Site of lesion

development

(9)

University of Tromsø – Faculty of Medicine uit.no

Differences in death of chronical diseases between Greenlands eskimoes and Danes

Stroke

Acute myocardial infarction Psoriasis

Diabetes Asthma

Thyrotoxicosis Multiple Sclerosis Epilepsia

Rheumatoid arthritis

2/1 1/10 1/20 Rare

1/25 Rare

0 2/1 Low

Kromann and Green, ACTA Med Scand 1980, 208, 401.

Eskimoes/Danes

(10)

University of Tromsø – Faculty of Medicine

MM-LDL

Proteoglycans

LDL

LDL LDL

LDL

Blood

Intima

Binding of LDL to PG in arterial intima:

l

Long LDL residence time (weeks versus min for other tissue)

l

High LDL conc

(10-fold higher than in other tissue)

LDL

LDL trapment in arterial intima

(11)

University of Tromsø – Faculty of Medicine uit.no

MM-LDL

Oxidative environment

MM- LDL

MM- LDL

Proteoglycans

Oxidation of trapped LDL:

l

Minimally modified LDL (MM-LDL)

l

Oxidized LDL (OX-LDL)

The oxidation may occur at low

speed.

LDL

LDL LDL

LDL

MM- LDL

LDL oxidation

(12)

University of Tromsø – Faculty of Medicine MM-

LDL

VCAM-1

MCP-1 M-CSF

MCP-1 Oxidized

lipids

Effects of minimally modified LDL

Monocyte and

endothelial release of

l

chemoattractant (MCP-1)

l

monocyte growth factor (M-CSF) Smooth muscle cell release of

l

chemoattractant (MCP-1)

P-selectin E-selectin ICAM-1

(13)

University of Tromsø – Faculty of Medicine uit.no

MM- LDL

MCP-1

MCP-1 Chemotaxic

stimuli

VCAM-1

Effects of minimally modified LDL

l

Adhesion of monocytes and T cells to

endothelium.

l

Migration of monocytes and T cells into intima.

Oxidized lipids

Adhesion

(14)

University of Tromsø – Faculty of Medicine MM-

LDL TNF-alpha

IL1-beta

Growth factors Foam

cell ROS

Chronic

inflammation

Macrophage

Effects of foam cells

Continued LDL oxidation

Continued influx of activated inflammatory cells leads to more advanced lesions.

Growth

factors

(15)

University of Tromsø – Faculty of Medicine uit.no

Extracellular lipid core

Atheroma

cholesterol

cholesterol ester

Advanced lesion

Lipid core formation

AHA

lesion

type IV

(16)

University of Tromsø – Faculty of Medicine

Advanced lesions

Smooth

Fibro-

atheroma

Intimal smooth muscles cause marked expansion of the intimal lesion due to

l

proliferation

l

collagen synthesis

l

fibrous cap formation

AHA lesion

type Va

(17)

University of Tromsø – Faculty of Medicine uit.no

Rupture of plaque

(18)

University of Tromsø – Faculty of Medicine

Effects of marine oils associated with reduction in

- inflammatory reactions

- atherogenesis (development of atherosclerosis) - thrombus formation

- depression - psoriasis

- inflammatory bowel disease (IBD)

-ADHD

(19)

University of Tromsø – Faculty of Medicine uit.no

Platelet activity

• Intake of marine oils reduces the activity of platelets (reduce platelet aggregation,

adhesion to vessel wall, generation of pro- inflammatory products)

• Important: Platelets are important in

thrombosis, atherosclerosis, myocardial

infarcts (MI), brain infarcts (stroke)

(20)

University of Tromsø – Faculty of Medicine

Oxidation rate of fatty acids depends largely on number of double bonds

? --

6 22:6 DHA

? --

5 20:5 EPA

2500 1.3

3 18:3

1200 19

2 18:2

100 82

1 18:1

1 --

- 18:0

Rel. rate of oxidation Induction

period (h) 25 C

Number of

double bonds

Fatty acid

(21)

University of Tromsø – Faculty of Medicine uit.no

• omega-3 fatty acids are also incorporated in LDL-particles

• particles are thereby more susceptible for oxidation

• increased lesion (atherosclerosis) formation in the vessel wall?

Adverse effects of omega-3 fatty acids?

(22)

University of Tromsø – Faculty of Medicine

History of clinical studies with marine oils in our laboratory

9 clinical studies

1986 Cod liver oil (CLO)

1987 Concentrate of EPA + DHA (85% , K85=Omacore)

1992 Cold pressed whale oil, refined seal oil, CLO, seal oil/CLO,

1994 Cold pressed and refined whale oils, CLO, seal oil/CLO, olive oil/CLO 1999 Smoked salmon, salmon filet, cod filet, CLO

1999 CLO products from various stages of refinement

2000 Cold pressed and refined whale oil, seal oil, and CLO 2003 Seal oil, CLO, Salmon pate, OliVita

2004 Salmon pate , CLO capsules

(23)

University of Tromsø – Faculty of Medicine uit.no

In our clinical studies on marine oils (9 studies) we had several interesting

observations:

-The beneficial effect of e.g. cold pressed whale oil was superior to cod liver oil despite

only half of the omega-3 fatty acids content -Refinement of marine oils removed a

large part of the beneficial effects

WHY: Removal of antioxidants and

quite possibly other unknown products

(24)

University of Tromsø – Faculty of Medicine

Administration of marine oils; 10 weeks

Parameter Control Seal Cod liver Seal+CL Whale

Serum: triacylglycerol (TG) - L* - - -

total cholesterol - - -

-

HDL cholesterol - - H* H***

Coagulation factors:

Prothrombin F1 + 2 - - -

L*

Lipopolysaccharide stimulated(LPS) whole blood:

tumornecrosis factor-αTNFα(monocytes) - - - L*

tissue factor activity (TF) (monocytes) - - L* L*

thromboxane B2 (TXB2) - - - L**

- no significance, L lower, H higher, * p< 0.05, ** p< 0.01, *** p< 0.005

Østerud et al., 1995 Lipids, 30 (12): 1111 - 1118

.

-

(25)

University of Tromsø – Faculty of Medicine uit.no

Seal oil studies

(26)

University of Tromsø – Faculty of Medicine

We have performed 4 clinical studies where intake of seal oil was one of the test

substances

Results: Similar effects as fish oil except that HDL-cholesterol (the positive cholesterol)

is more enhanced with seal oil compared

to fish oil and uptake of omega-3 fatty acids

from seal oil is better compared to fish oil

(27)

University of Tromsø – Faculty of Medicine uit.no

Seal oil study in Canada i 1999 (Conquer et al. 96: 239-50)

20 g seal oil per day in capsules for 6 weeks

Results: 2.7 to 4.3 times increase in EPA, and DHA increased between 1.5 to 2.4 times.

DPA increased 0.5 to 0.7 times

Pro-inflammatory fatty acid arachidonic acids was reduced by 26%

Fibrinogen- a protein associated with risk of

coronary heart disease was reduced by 18%

(28)

University of Tromsø – Faculty of Medicine

Murphy et al 1999; (Lipids 34: 115-24)

Another study from Canada showed that Guinea pigs had a higher rise in omega-3

fatty acids with seal oil compared to fish oil

Reduced production of thromboxane A 2 , a

product that makes the platelets more sticky,

with both marine oils

(29)

University of Tromsø – Faculty of Medicine uit.no

Bonefeld-Jorgensen et al 2001 (Int J Circumpolar Health, 60: 25-33.

10 capsules seal oil per day in 10 persons for 6.

5 capsules seal oil per day in 5 persons for 6 weeks.

Positive changes in fatty acid composition regarding ratio between n-6 and n-3 fatty acids.

Positive effects on an inflammatory product

in lymphocytes.

(30)

University of Tromsø – Faculty of Medicine

Studies from Bergen:

Brunborg LA Clin Nutr. 2008 Mar 26. [Epub ahead of print]

“Effects of short-term oral

administration of dietary marine oils in patients with inflammatory bowel

disease and joint pain: A pilot study comparing seal oil and cod liver oil”

CONCLUSION: No significant differences

in the two treatment groups were seen; in

both groups, the changes in several joint

pain parameters, leukotriene B(4) level of

plasma, and serum fatty acid profile were

putatively favorable.

(31)

University of Tromsø – Faculty of Medicine uit.no

Development of a new oil mixture

(32)

University of Tromsø – Faculty of Medicine

A combination of seal oil and cold pressed olive oil (OliVita)

OliVita has all the positive effects of omega-3 fatty acids; but even more important, excessive antioxidants/anti- inflammatory products

that together with the omega-3 fatty acids, prevent inflammatory reactions

Designed to have similar effects as cold

pressed whale oil!

(33)

University of Tromsø – Faculty of Medicine uit.no

The stability of various oils when heated to The stability of various oils when heated to The stability of various oils when heated to The stability of various oils when heated to

70 70

70 70 oooo C C C C and exposed to oxidation and exposed to oxidation and exposed to oxidation and exposed to oxidation

Oil Hours before start ”Second”

reaction

of oxidation Seal oil + olive oil 38

Fish oil + olive oil 23

Olive oil > 60

Soya oil 1.1

Cod liver oil (CLO) 0.5 9.6

Seal oil 2.1 12.5

Conc. EPA+DHA < 5 min

(34)

University of Tromsø – Faculty of Medicine

Diet added 15 ml cod liver oil (CLO), OliVita or nothing (Control), % changes in parameters related to coronary heart disese (CHD) before and after intake.

Groups HDL-- chol

hsCRP MCP-1 TxB2 LTB4

Control 0 +5.1 +8.5 0 +36.6

CLO +1.4

(i.s.)

+12.5 (n.s.)

-5.2 (0.05)

-14.3 (0.05)

+8.6 (0.001)

OliVita +8.3 (0.05)

-24.0 (0.001)

-14.3 (0.005)

-17.6 (0.05)

+8.8

(0.001)

(35)

University of Tromsø – Faculty of Medicine uit.no

Studies on transgenic mice

Knock out mice (transgenic), who acquire rapidly atherosclerosis were used to detect the effects of dietary oils.

By supplying the diet with various oils we can measure the effect by the quantification of the fatty plaques formed on the vessel wall in these animals.

This gives us a final proof whether the oils may have a beneficial effect on the

development of atherosclerosis.

(36)

University of Tromsø – Faculty of Medicine

(37)

University of Tromsø – Faculty of Medicine uit.no

(38)

University of Tromsø – Faculty of Medicine

(39)

University of Tromsø – Faculty of Medicine uit.no

Plaque burden – aortic arch

4,40

11,86

10,99 10,46

15,01

12,50

0 5 10 15 20

Females Males

Plaque burden (% of aortic area)

Seal-Oliv Corn No oil

*

(40)

University of Tromsø – Faculty of Medicine

Eskimo advice

Eskimo advice - - for obvious reasons this may not be for obvious reasons this may not be perceived as an alternative

perceived as an alternative… …. .

”Every day you should eat something from each of the five basic food groups;

fried blubber, boiled blubber, stewed

blubber, baked blubber

and raw blubber”

(41)

University of Tromsø – Faculty of Medicine uit.no

Conclusion:

Eat more seafood and supplement it

with a combination of seal oil and olive oil

that will provide sufficient antioxidants to

prevent inflammatory reactions in your

body.

(42)

University of Tromsø – Faculty of Medicine

Thank you for your attention!

(43)

University of Tromsø – Faculty of Medicine uit.no

What causes cardiovascular diseases?

-Inheritance

-High LDL-cholesterol and low HDL-cholesterol -Diabetes

-High blood pressure

-Lack of physical activity -Smoking

-Overweight

Amplifying factors:

-milieu-social status -bacteria

-unhealthy diet

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