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Nytta och risk med konsumtion av fet fisk
Uppsala, okt.2002
Jørn DyerbergJørn Dyerberg
Hjärta/kärlaspekter, Hjärta/kärlaspekter,
omega-3-fettsyroromega-3-fettsyror
Age standardised death rates in per cent of all deaths from IHD in males aged 45-64 yearsFigures in Greenland based on the years 1974-76.
IHD deathsIHD deaths
U.S.U.S. 40,440,4
DenmarkDenmark 34,734,7
GreenlandGreenland 5,35,3
Lancet 1971; 1:1143-6
Fatty acid composition of plasma phospholipids in Greenland Eskimos GE and Danish controls D. Values are means as per cent of total (Am J Clin Nutr 1975;28:958-66)
GEGE DD
8:0 – 15:08:0 – 15:0 4.24.2 0.30.3
16:016:0 32.232.2 30.030.0
16:116:1 4.34.3 0.80.8
16:2 – 17:116:2 – 17:1 -- 0.70.7
18:018:0 17.017.0 14.614.6
18:118:1 14.914.9 12.412.4
18:218:2 5.45.4 22.322.3
18:318:3 0.10.1 0.20.2
18:4 – 20:318:4 – 20:3 3.33.3 0.70.7
20:420:4 3.83.8 7.47.4
20:520:5 7.47.4 1.81.8
22:0 – 22:522:0 – 22:5 2.22.2 2.22.2
22:622:6 3.63.6 2.22.2
24:0 – 24:124:0 – 24:1 2.52.5 4.24.2
SaturatedSaturated 54.554.5 47.347.3
MonoenesMonoenes 24.424.4 15.315.3
PolyenesPolyenes 21.121.1 34.234.2
20:5/20:420:5/20:4 1.951.95 0.240.24
Lancet 1978; 2:1179
Distribution of fatty acid classes in Danish and Eskimo food and blood platelets
FoodFood
Omega-6 class__________________________________Omega-6 class__________________________________
Omega-3 class__________________________________Omega-3 class__________________________________
PlateletsPlatelets
Arachidonic acid (Omega-6)_______________________Arachidonic acid (Omega-6)_______________________
Eicosapentaenoic acid (Omega-3)___________________Eicosapentaenoic acid (Omega-3)___________________
Bleeding Time_____________________________________Bleeding Time_____________________________________
EskimosEskimos5,4 g/day5,4 g/day
13,7 g/day13,7 g/day
8,5 %8,5 %8,0 %8,0 %
8,1 min8,1 min
DanesDanes10,0 g/day10,0 g/day2,8 g/day2,8 g/day
22,1 %22,1 %0,5 %0,5 %
4,7 min4,7 min
Lancet 1979;2:433-5
The effect of n-3 PUFA supplementation on bleeding time (BT) in normals and different patient groups
n-3 PUFAn-3 PUFA DurationDuration Median BT (min)Median BT (min)
Patient groupPatient group nn g/day g/day (weeks)(weeks) beforebefore afterafter p valuep value
Angina pectorisAngina pectoris11 3636 4.54.5 1212 55 5½5½ N.S.N.S.
IDDMIDDM22 1010 44 66 55 5½5½ 0.05<p<0.100.05<p<0.10
HyperlipemiaHyperlipemia33 1717 66 66 55 66 <0.05<0.05
HypertensionHypertension44 1010 44 66 66 6½6½ N.S.N.S.
NormalsNormals55 1010 44 66 55 6½6½ <0.05<0.05
NormalNormal66 2020 44 44 55 5½5½ <0.05<0.05
1.1. Kristiansen et al. Atherosclerosis 1987; 13-9Kristiansen et al. Atherosclerosis 1987; 13-92.2. Schmidt et al. J Intern Med 1989; (suppl 1) : 201-6Schmidt et al. J Intern Med 1989; (suppl 1) : 201-63.3. Schmidt et al. Thromb Haemostas 1989; 62: 797-801Schmidt et al. Thromb Haemostas 1989; 62: 797-8014.4. Schmidt et al. Clin Chim Acta 1990; 189; 25-32Schmidt et al. Clin Chim Acta 1990; 189; 25-325.5. Schmidt et al. Thromb Haemostas 1990; 63: 1-5Schmidt et al. Thromb Haemostas 1990; 63: 1-56.6. Mortensen et al. Thromb Haemostas 1983; 30: 543-6. Mortensen et al. Thromb Haemostas 1983; 30: 543-6.
Gissi-Prevenzione trial
2830 given n-3 PUFAplus vitamin E
11324 patients randomised
3 lost to follow-up768 discontinued
n-3 PUFA
4 lost to follow-up687 discontinued
vitamin E11 receivedn-3 PUFA
4 lost to follow-up848 discontinued
n-3 PUFA808 discontinued
vitamin E
2 lost to follow-up15 receivedn-3 PUFA2 receivedvitamin E
2836 analysedfor outcomes
2830 analysedfor outcomes
2830 analysedfor outcomes
2828 analysedfor outcomes
2828controls
2830 given vitamin E2830 given n-3 PUFA
Lancet 1999; 354: 447-55
Figure 1: Trial profile
GISSI – Preventione TrialResults (RR Four-way analysis)
n-PUFAn-PUFA
All fatal eventsAll fatal events 0.80 (p = 0.008)0.80 (p = 0.008)
CV deathsCV deaths 0.70 (p = 0.0242)0.70 (p = 0.0242)
Sudden deathSudden death 0.55 (0 = 0.010)0.55 (0 = 0.010)
Death, non-fatal MI, and non-fatal Death, non-fatal MI, and non-fatal strokestroke
0.85 (p = 0.023)0.85 (p = 0.023)
Cardiovascular death, non-fatal MI, Cardiovascular death, non-fatal MI, and nonfatal strokeand nonfatal stroke
0.80 (p = 0.008)0.80 (p = 0.008)
Lancet 1999;Lancet 1999; 254254: 4475-54475-5
Heart Rate Variability
Standards of Measurement, Physiological Interpretation, and Clinical Use
Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology
“Because 24-hour HRV indices appear to be stable and free of placebo effect, they may be ideal variables to assess intervention therapies”
“A powerful predictor of SCD”
Circulation 1996;93:1043
Special Report
Lav HFV
Høj HFV
Omega-3 fedtsyrer og pludselig hjertedød
DHA i trombocytterlav mellem høj
(Am J Cardiol 1997;79:1670)
Patienter med AMI og EF < 0.40
80
120
160SDNN (ms)
1. kvartil 2.-3. kvartil 4. kvartil
HRV and DHA in healthy men
r = 0.50, p<0.01r = 0.50, p<0.01---------Lowess ---------Lowess regressionregression______linear regression______linear regression
r = 0.68, p<0.001 in the r = 0.68, p<0.001 in the interval 1.3<DHA<2.1interval 1.3<DHA<2.1
Content of DHA in granulocytesContent of DHA in granulocytes
Am J Clin Nutr 1999;70:333-7
H R V in H e a lth y M en w ith a b a se lin e S D N N < 1 5 0 m s
1 2 0
1 2 5
1 3 0
1 3 5
1 4 0
1 4 5
1 5 0
2 .0 g o f O m e g a -3 fa t ty a c id s 6 .6 g o f O m e g a -3 fa tty a c id s
= b e fo re
= a fte r
*S D N N (m s)
Am J Clin Nutr 1999;70:331-7
Marine n-3 Fatty Acids, Wine Intake, and Heart RateVariability in Patients Referred for Coronary Angiography
Circulation 2001;103:651
295 patients referred for elective coronary angiography
Food questionnaire and drinking habits
Adipose tissue biopsy (n-3 fatty acids)
Granulocytes and platelets (n-3 fatty acids)
24-hour HRV
Table 2. Fish Consumption (Fish Score) Related to n-3 PUFA Levels
Fish ScoreFish Score
2-42-4
(n=29)(n=29)
5-65-6
(n=49)(n=49)
7-87-8
(n=91)(n=91)
9-109-10
(n-113)(n-113)
11-1211-12
(n=19)(n=19)
GranulocytesGranulocytes
EPA, %EPA, % 0.63 (0.3)0.63 (0.3) 0.68 (0.3)0.68 (0.3) 0.77 (0.4)0.77 (0.4) 1.02 (0.5)1.02 (0.5) 1.12 (0.5)*1.12 (0.5)*
DHA, %DHA, % 1.34 (0.4)1.34 (0.4) 1.52 (0.4)1.52 (0.4) 1.59 (0.4)1.59 (0.4) 1.88 (0.5)1.88 (0.5) 1.81 (0.5)*1.81 (0.5)*
Total n-3Total n-3
PUFA %PUFA %
3.30 (0.8)3.30 (0.8) 3.56 (1.0)3.56 (1.0) 3.82 (1.0)3.82 (1.0) 4.56 (1.3)4.56 (1.3) 4.41 (1.2)*4.41 (1.2)*
Adipose tissueAdipose tissue
EPA, %EPA, % 0.09 (0.04)0.09 (0.04) 0.11 (0.04)0.11 (0.04) 0.12 (0.05)0.12 (0.05) 0.14 (0.05)0.14 (0.05) 0.16 (0.05)*0.16 (0.05)*
DHA, %DHA, % 0.23 (0.09)0.23 (0.09) 0.30 (0.12)0.30 (0.12) 0.34 (0.14)0.34 (0.14) 0.40 (0.16)0.40 (0.16) 0.46 (0.18)*0.46 (0.18)*
Total n-3Total n-3
PUFA %PUFA %
0.60 (0.19)0.60 (0.19) 0.71 (0.23)0.71 (0.23) 0.79 (0.25)0.79 (0.25) 0.88 (0.29)0.88 (0.29) 0.96 (0.29)*0.96 (0.29)*
The mean levels (SD) of the n-3 PUFA eicosapentaenoic acid (EPA) and DHA in granulocyte The mean levels (SD) of the n-3 PUFA eicosapentaenoic acid (EPA) and DHA in granulocyte membranes and in adipose tissue are givenmembranes and in adipose tissue are given
*p<0.001 (Kruskal-Wallis test)*p<0.001 (Kruskal-Wallis test)
Cirkulation 2001; 103: 651-7Cirkulation 2001; 103: 651-7
Table 3. Univariate Nonparametric Correlation Coefficients Between Levels of n-3 PUFA in Adipose Tissue and in Granulocyte Membranes and HRV Indices in the 291 Patients
Adipose TissueAdipose Tissue Granulocyte MembranesGranulocyte Membranes
EPAEPA DHADHA Total n-3 PUFATotal n-3 PUFA EPAEPA DHADHA Total n-3 PUFATotal n-3 PUFA
RRRR 0.0870.087 0.121*0.121* 0.124*0.124* 0.130*0.130* 0.1660.166†† 1.150*1.150*
SDNNSDNN -0.002-0.002 0.0440.044 0.0280.028 0.0880.088 0.150*0.150* 0.132*0.132*
SDNN SDNN indexindex
0.0480.048 0.122*0.122* 0.1010.101 0.167 0.167 †† 0.214 0.214 †† 0.191 0.191 ††
SDANN SDANN indexindex
-0.012-0.012 0.0100.010 0.0000.000 0.0630.063 0.124*0.124* 0.1130.113
RMSSDRMSSD 0.0330.033 0.138*0.138* 0.1150.115 0.0830.083 0.152*0.152* 0.1010.101
PNN50PNN50 0.0350.035 0.1340.134 0.1140.114 0.0710.071 0.137*0.137* 0.0840.084
**pp<0.05; <0.05; ††pp<0.01<0.01
Cirkulation 2001; 103: 651-7Cirkulation 2001; 103: 651-7
**: p<0.01, Kruskall-Wallis test
**: p<0.01, Kruskall-Wallis test
**: p<0.01, Kruskall-Wallis test
Table 5. Linear Multiple Regression Analysis (Backward) With HRV Indices as Dependent Factors
Modifiable FactorsModifiable FactorsNonmodifiableNonmodifiable
FactorsFactorsMedicationMedication n-3 PUFA Relatedn-3 PUFA Related LifestyleLifestyle
RRRR -Blocker-Blocker†† DHA(g), DHA(g), † n-3 PUFA(a)*† n-3 PUFA(a)* Tobacco Tobacco †† Age Age ††
SDNNSDNN -Blocker*-Blocker* DHA(g)*DHA(g)* Tobacco Tobacco †† MI*MI*
SDNNindexSDNNindexDHA(g), DHA(g), † n-3 PUFA(g),*† n-3 PUFA(g),*
EPA(g),* EPA(a)*EPA(g),* EPA(a)*Tobacco Tobacco ††
SCANNindexSCANNindex -Blocker -Blocker †† DHA(g)*DHA(g)* Tobacco Tobacco ††
RMSSDRMSSD -Blocker*-Blocker*EPA(a), EPA(a), † n-3 PUFA(a), † † n-3 PUFA(a), †
EPA(g)*EPA(g)*Age*Age*
PNN50PNN50 -Blocker*-Blocker*EPA(g),* DHA(g),* EPA(a), EPA(g),* DHA(g),* EPA(a), †, n-†, n-
3 PUFA(a) †3 PUFA(a) †
Backward linear multiple regression analysis was conducted with the following independent Backward linear multiple regression analysis was conducted with the following independent modifiable factors: (1) body mass index; medical therapy with (2) ACE inhibitors, (3) modifiable factors: (1) body mass index; medical therapy with (2) ACE inhibitors, (3) -blockers, or -blockers, or (4) calcium inhibitors; (5) wine intake; (6) tobacco use; (7) EPA in granulocytes [EPA(g)]; (8) DHA in(4) calcium inhibitors; (5) wine intake; (6) tobacco use; (7) EPA in granulocytes [EPA(g)]; (8) DHA in granulocytes [DHA(g)]; (9) total n=3 PUFAs in granulocytes [PUFA(g)]; (10) EPA in adipose granulocytes [DHA(g)]; (9) total n=3 PUFAs in granulocytes [PUFA(g)]; (10) EPA in adipose tissue[EPA(a)]; (11) DHA in adipose tissue [DHA(a)]; and (12) total n=3 PUFAs in adipose tissue tissue[EPA(a)]; (11) DHA in adipose tissue [DHA(a)]; and (12) total n=3 PUFAs in adipose tissue [PUFA(a)]. Nonmodifiable factors included in the test were (13) age, (14) left ventricular ejection [PUFA(a)]. Nonmodifiable factors included in the test were (13) age, (14) left ventricular ejection fraction, (15) previous MI, (16) sex, and (17) the extent of coronary artery disease. Significant fraction, (15) previous MI, (16) sex, and (17) the extent of coronary artery disease. Significant independent factors are given.independent factors are given.
Cirkulation 2001; 103: 651-7
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