Oméga-3:
faits - thérapeutique et posologie
Infarctus
du myocarde: 1,0g/jour EPA et DHA en prévention secondaire
Les journaux spécialisés ont consacré
aux oméga-3 les articles suivants. La liste de ces publications
a été établie en avril 2003 et n'aspire nullement
à l'exhaustivité. Source: MEDLINE.
Ces données servent de référence pour les
médecins et les thérapeutes, de sorte à déterminer
la dose thérapeutique dans le cadre de l'infarctus du
myocarde.
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n-3
polyunsaturated fatty acids and cardiovascular diseases.
Nordøy A: Department of Medicine, University of Tromsø,
Norway; Marchioli R, Arnesen H, Videbaek J
Lipids 2001 36 Suppl:S127-9
Abstract
An expert round table discussion on the relationship between intake
of n-3 polyunsaturated fatty acids (PUFA) mainly of marine sources
and coronary heart disease at the 34th Annual Scientific Meeting
of European Society for Clinical Investigation came to the following
conclusions: 1. Consumption of 1-2 fish meals/wk is associated
with reduced coronary heart disease (CHD) mortality. 2.
Patients who have experienced myocardial infarction have decreased
risk of total, cardiovascular, coronary, and sudden death by drug
treatment with 1 g/d of ethylesters of n-3 PUFA, mainly as eicosapentaenoic
acid (EPA) and docosahexaenoic acid (DHA). The effect
is present irrespective of high or low traditional fish intake
or simultaneous intake of other drugs for secondary CHD prevention.
n-3 PUFA may also be given as fatty fish or triglyceride concentrates.
3. Patients who have experienced coronary artery bypass surgery
with venous grafts may reduce graft occlusion rates by administration
of 4 g/d of n-3 PUFA. 4. Patients with moderate hypertension may
reduce blood pressure by administration of 4 g/d of n-3 PUFA.
5. After heart transplantation, 4 g/d of n-3 PUFA may protect
against development of hypertension. 6. Patients with dyslipidemia
and or postprandial hyperlipemia may reduce their coronary risk
profile by administration of 1-4 g/d of marine n-3 PUFA. The
combination with statins seems to be a potent alternative in these
patients. 7. There is growing evidence that daily intake of up
to 1 energy% of nutrients from plant n-3 PUFA (alpha-linolenic
acid) may decrease the risk for myocardial infarction and death
in patients with CHD. This paper summarizes the conclusions of
an expert panel on the relationship between n-3 PUFA and CHD.
The objectives for the experts were to formulate scientifically
sound conclusions on the effects of fish in the diet and the administration
of marine n-3 PUFA, mainly eicosapentaenoic acid (EPA, 20:5n-3)
and docosahexaenoic acid (DHA, 22:6n-3), and eventually of plant
n-3 PUFA, alpha-linolenic acid (ALA, 18:3n-3), on primary and
secondary prevention of CHD. Fish in the diet should be considered
as part of a healthy diet low in saturated fats for everybody,
whereas additional administration of n-3 PUFA concentrates could
be given to specific groups of patients. This workshop was organized
on the basis of questions sent to the participants beforehand,
on brief introductions by the participants, and finally on discussion
and analysis by a group of approximately 40 international scientists
in the fields of nutrition, cardiology, epidemiology, lipidology,
and thrombosis.
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n-3
Polyunsaturated fatty acids, fatal ischemic heart disease, and
nonfatal myocardial infarction in older adults: the Cardiovascular
Health Study.
Lemaitre RN: Cardiovascular Health
Research Unit, Department of Medicine, University of Washington,
Seattle, USA; King IB, Mozaffarian D, Kuller LH,
Tracy RP, Siscovick DS
Am J Clin Nutr 2003 Feb 77:319-25
Abstract
BACKGROUND: Little is known about the relation of the
dietary intake of n-3 polyunsaturated fatty acids, ie, docosahexaenoic
acid (DHA) and eicosapentaenoic acid (EPA) from fatty fish and
alpha-linolenic acid from vegetable oils, with ischemic heart
disease among older adults. OBJECTIVE: We investigated the associations
of plasma phospholipid concentrations of DHA, EPA, and alpha-linolenic
acid as biomarkers of intake with the risk of incident fatal ischemic
heart disease and incident nonfatal myocardial infarction in older
adults. DESIGN: We conducted a case-control study nested in the
Cardiovascular Health Study, a cohort study of adults aged
> or = 65 y. Cases experienced incident fatal myocardial
infarction and other ischemic heart disease death (n = 54)
and incident nonfatal myocardial infarction (n = 125).
Matched controls were randomly selected (n = 179). We measured
plasma phospholipid concentrations of n-3 polyunsaturated fatty
acids in blood samples drawn approximately 2 y before the event.
RESULTS: A higher concentration of combined DHA and EPA was
associated with a lower risk of fatal ischemic heart disease,
and a higher concentration of alpha-linolenic acid with a tendency
to lower risk, after adjustment for risk factors [odds ratio:
0.32 (95% CI: 0.13, 0.78; P = 0.01) and 0.52 (0.24, 1.15; P =
0.1), respectively]. In contrast, n-3 polyunsaturated fatty acids
were not associated with nonfatal myocardial infarction. CONCLUSIONS:
Higher combined dietary intake of DHA and EPA, and possibly alpha-linolenic
acid, may lower the risk of fatal ischemic heart disease in older
adults. The association of n-3 polyunsaturated fatty acids
with fatal ischemic heart disease, but not with nonfatal myocardial
infarction, is consistent with possible antiarrhythmic effects
of these fatty acids.
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Effects
of supplementation with fish oil-derived n-3 fatty acids and gamma-linolenic
acid on circulating plasma lipids and fatty acid profiles in women.
Laidlaw M: Department of Human Biology
and Nutritional Sciences, University of Guelph, Canada; Holub BJ
Am J Clin Nutr 2003 Jan 77:37-42
Abstract
BACKGROUND: Eicosapentaenoic acid (EPA), docosahexaenoic
acid (DHA), and gamma-linolenic acid (GLA) have lipid-modifying
and antiinflammatory properties. The effects of supplement mixtures
of these fatty acids on plasma lipids and the fatty acid compositions
of serum phospholipids have received little attention. OBJECTIVE:
The objective was to determine the effects of different levels
of GLA supplementation together with a constant intake of EPA
plus DHA on the triacylglycerol-lowering effect of EPA plus DHA
alone and on the fatty acid patterns (eicosanoid precursors) of
serum phospholipids. DESIGN: Thirty-one women were assigned
to 1 of 4 groups, equalized on the basis of their fasting triacylglycerol
concentrations. They received supplements providing 4 g EPA+DHA
(4:0, EPA+DHA:GLA; control group), 4 g EPA+DHA plus 1 g
GLA (4:1), 2 g GLA (4:2), or 4 g GLA (4:4) daily for 28
d. Plasma lipids and fatty acids of serum phospholipids were measured
on days 0 and 28. RESULTS: Plasma triacylglycerol concentrations
were significantly lower on day 28 than on day 0 in the 4:0, 4:1,
and 4:2 groups. LDL cholesterol decreased significantly (by
11.3%) in the 4:2 group. Dihomo-gamma-linolenic acid increased
significantly in serum phospholipids only in the 4:2 and 4:4 groups;
however, total n-3 fatty acids increased in all 4 groups. CONCLUSIONS:
A mixture of 4 g EPA+DHA and 2 g GLA favorably altered blood lipid
and fatty acid profiles in healthy women. On the basis of calculated
PROCAM values, the 4:2 group was estimated to have a 43% reduction
in the 10-y risk of myocardial infarction.
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Serum
free fatty acid pattern and risk of myocardial infarction: a case-control
study.
Yli-Jama P: Institute for Nutrition
Research, Medical Faculty, University of Oslo, Norway; Meyer HE,
Ringstad J, Pedersen JI
J Intern Med 2002 Jan 251:19-28
Abstract
OBJECTIVES: To investigate the association
between composition of serum free fatty acid (FFA) fraction and
risk of a first myocardial infarction (MI). DESIGN: A case-control
design. SETTING: The patients were recruited from Ullevö Hospital
in Oslo and Ostfold Central Hospital in Fredrikstad and Sarpsborg,
Norway. SUBJECTS: A total of 103 patients with first MI and
104 population controls, both men and postmenopausal women, age
45-75 years. RESULTS: The mean molar percentage content of docosahexaenoic
(DHA), eicosapentaenoic (EPA), stearic and myristic acid in the
serum FFA fraction was significantly lower in cases than in controls,
whereas that of oleic and linoleic acid was higher in cases.
Increased percentage content of total very long-chain omega-3 fatty
acids (VLC n-3) in serum FFA was associated with decreased risk
of MI. Multivariate odds ratio (OR), adjusted for age, sex,
waist-hip ratio, smoking, family history of coronary heart disease
(CHD) and years of education was 0.20 (95% CI 0.06-0.63) for the
highest vs. lowest quartile. Also increased content of stearic acid
was associated with decreased risk. Multivariate OR adjusted as
above was 0.38 (95% CI 0.14-1.04) for the highest versus lowest
quartile. After adjustment for oleic acid, however, the inverse
linear trend was no longer significant. CONCLUSIONS: The percentage
content of VLC n-3 as well as of stearic acid in serum FFA was inversely
associated with risk of myocardial infarction. That of VLC n-3 may
reflect diet, but additionally these free fatty acids might in some
way be related to the pathogenetic process and not only reflect
their content in adipose tissue. |
Influence
of highly concentrated n-3 fatty acids on serum lipids and hemostatic
variables in survivors of myocardial infarction receiving either
oral anticoagulants or matching placebo.
Smith P, Arnesen H, Opstad T,
Dahl KH, Eritsland J
Thromb Res 1989 Mar 53:467-74
Abstract
Forty patients with previous myocardial
infarction were given 4 capsules with 1 g concentrated fish oil
preparation daily for 4 weeks. No special diet was applied.
The supplementation was equivalent to 3.4 grams of eicosapentaenoic
acid (EPA) and docosahexaenoic acid (DHA) daily. Twenty-two
of the 40 subjects received concomitant treatment with long-term
oral anticoagulants (OAC). The fatty acid composition of serum after
the supplementation period showed a significant increase in the
proportion of EPA and DHA, while arachidonic acid (AA) remained
essentially constant. This resulted in a rise of the EPA/AA ratio
from 0.59 to 1.49 (p less than 0.001), confirming satisfying absorption
of the concentrate. Blood lipids showed an overall decrease of
triglycerides (TG) by 25% (p = 0.02), while total cholesterol rose
by 5% (p = 0.03) and HDL-cholesterol was unaffected. Blood glucose
and the TG associated factors plasminogen activator inhibitor and
factor VII-phospholipid complex revealed trends towards reduction.
Ivy bleeding time showed a significant prolongation, the median
increasing from 240 to 270 seconds. A significant increase of fibrinogen
was seen, as was a decrease of clotting time in the combined prothrombin
test in patients receiving concomitant OAC. Thus, given for 4 weeks,
the investigated concentrate of n-3 fatty acids exerts not merely
beneficial effects as far as the risk profile for atherosclerotic
disease is concerned. The results also point towards interactions
with OAC that may be of clinical relevance |
Health
benefits of docosahexaenoic acid (DHA)
Horrocks LA: Docosa Foods Ltd, Columbus,
OH, USA; Yeo YK
Pharmacol Res 1999 Sep 40:211-25
Abstract
Docosahexaenoic acid (DHA) is essential for
the growth and functional development of the brain in infants. DHA
is also required for maintenance of normal brain function in adults.
The inclusion of plentiful DHA in the diet improves learning ability,
whereas deficiencies of DHA are associated with deficits in learning.
DHA is taken up by the brain in preference to other fatty acids.
The turnover of DHA in the brain is very fast, more so than is generally
realized. The visual acuity of healthy, full-term, formula-fed infants
is increased when their formula includes DHA. During the last 50
years, many infants have been fed formula diets lacking DHA and
other omega-3 fatty acids. DHA deficiencies are associated with
foetal alcohol syndrome, attention deficit hyperactivity disorder,
cystic fibrosis, phenylketonuria, unipolar depression, aggressive
hostility, and adrenoleukodystrophy. Decreases in DHA in the brain
are associated with cognitive decline during aging and with onset
of sporadic Alzheimer disease. The leading cause of death in western
nations is cardiovascular disease. Epidemiological studies have
shown a strong correlation between fish consumption and reduction
in sudden death from myocardial infarction. The reduction
is approximately 50% with 200 mg day(-1)of DHA from fish. DHA is
the active component in fish. Not only does fish oil reduce triglycerides
in the blood and decrease thrombosis, but it also prevents cardiac
arrhythmias. The association of DHA deficiency with depression
is the reason for the robust positive correlation between depression
and myocardial infarction. Patients with cardiovascular disease
or Type II diabetes are often advised to adopt a low-fat diet with
a high proportion of carbohydrate. A study with women shows that
this type of diet increases plasma triglycerides and the severity
of Type II diabetes and coronary heart disease. DHA is present in
fatty fish (salmon, tuna, mackerel) and mother's milk. DHA is present
at low levels in meat and eggs, but is not usually present in infant
formulas. EPA, another long-chain n-3 fatty acid, is also present
in fatty fish. The shorter chain n-3 fatty acid, alpha-linolenic
acid, is not converted very well to DHA in man. These longchain
n-3 fatty acids (also known as omega-3 fatty acids) are now becoming
available in some foods, especially infant formula and eggs in Europe
and Japan. Fish oil decreases the proliferation of tumour cells,
whereas arachidonic acid, a longchain n-6 fatty acid, increases
their proliferation. These opposite effects are also seen with inflammation,
particularly with rheumatoid arthritis, and with asthma. DHA has
a positive effect on diseases such as hypertension, arthritis, atherosclerosis,
depression, adult-onset diabetes mellitus, myocardial infarction,
thrombosis, and some cancers. |
The
Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardio
(GISSI)-Prevenzione Trial on fish oil and vitamin E supplementation
in myocardial infarction survivors.
Stone NJ: Northwestern University School
of Medicine, Chicago, IL, USA
Curr Cardiol Rep 2000 Sep 2:445-51
Abstract
A recent large-scale, open-label, randomized,
controlled trial in 11, 324 myocardial
infarction (MI) survivors has shown low-dose
fish oil, but not vitamin E, to reduce significantly the cumulative
rate of all-cause death, nonfatal MI, and nonfatal stroke.
Neither intervention significantly reduced the other primary endpoint,
the cumulate rate of cardiovascular death, nonfatal MI, and nonfatal
stroke. Analysis of secondary endpoints indicated that the
benefits of the 875 mg fish oil capsules containing 850 to 882
mg eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) as
ethyl esters was in reducing mortality and not in a reduction of
nonfatal MI. It was a safe intervention. The internal
validity and external validity of the data was examined and the
findings placed in clinical perspective. Important questions remain
about the benefits of increased plant sources of n-3 polyunsaturated
fatty acids (PUFA) for those who cannot obtain or consume fish.
Also the benefits of diet versus fish oil supplementation haven't
been determined precisely. Although it
seems reasonable to increase sources of n-3 PUFA in the diet for
those at high risk of coronary heart disease, current
data do not support a policy of promoting fish oil capsules for
secondary prevention of coronary heart disease |
Dietary
supplementation with n-3 polyunsaturated fatty acids and vitamin
E after myocardial infarction: results of the GISSI-Prevenzione
trial.
Valagussa F and the Gruppo Italiano per lo Studio della Sopravvivenza
nell'Infarto miocardico
Lancet 1999 354:447-455
Abstract
BACKGROUND: There is conflicting evidence on the benefits of foods
rich in vitamin E (alpha-tocopherol), n-3 polyunsaturated fatty
acids (PUFA), and their pharmacological substitutes. We investigated
the effects of these substances as supplements in patients who had
myocardial infarction. METHODS: From October, 1993, to September,
1995, 11,324 patients surviving recent (< or = 3 months) myocardial
infarction were randomly assigned supplements of n-3 PUFA (1 g daily,
n=2836), vitamin E (300 mg daily, n=2830), both (n=2830), or none
(control, n=2828) for 3.5 years. The primary combined efficacy endpoint
was death, non-fatal myocardial infarction, and stroke. Intention-to-treat
analyses were done according to a factorial design (two-way) and
by treatment group (four-way). FINDINGS: Treatment with n-3 PUFA,
but not vitamin E, significantly lowered the risk of the primary
endpoint (relative-risk decrease 10% [95% CI 1-18] by two-way analysis,
15% [2-26] by four-way analysis). Benefit was attributable to a
decrease in the risk of death (14% [3-24] two-way, 20% [6-33] four-way)
and cardiovascular death (17% [3-29] two-way, 30% [13-44] four-way).
The effect of the combined treatment was similar to that for n-3
PUFA for the primary endpoint (14% [1-26]) and for fatal events
(20% [5-33]). INTERPRETATION: Dietary supplementation with n-3 PUFA
led to a clinically important and statistically significant benefit.
Vitamin E had no benefit. Its effects on fatal cardiovascular events
require further exploration. |
Intake
of fish and omega-3 fatty acids and risk of stroke in women.
Iso H: Division of Preventive Medicine, Brigham and Women's Hospital,
Boston MA, USA; Rexrode KM, Stampfer MJ, Manson JE, Colditz GA,
Speizer FE, Hennekens CH, Willett WC
JAMA 2001 Jan 285:304-12
Abstract
CONTEXT: Some prospective studies have shown an inverse association
between fish intake and risk of stroke, but none has examined the
relationship of fish and omega-3 polyunsaturated fatty acid intake
with risk of specific stroke subtypes. OBJECTIVE: To examine the
association between fish and omega-3 polyunsaturated fatty acid
intake and risk of stroke subtypes in women. DESIGN, SETTING, AND
SUBJECTS: Prospective cohort study of women in the Nurses'
Health Study cohort, aged 34 to 59 years in 1980, who were
free from prior diagnosed cardiovascular disease, cancer, and history
of diabetes and hypercholesterolemia and who completed a food frequency
questionnaire including consumption of fish and other frequently
eaten foods. The 79 839 women who met our eligibility criteria
were followed up for 14 years. MAIN OUTCOME MEASURE: Relative
risk of stroke in 1980-1994 compared by category of fish intake
and quintile of omega-3 polyunsaturated fatty acid intake. RESULTS:
After 1 086 261 person-years of follow-up, 574 incident strokes
were documented, including 119 subarachnoid hemorrhages, 62 intraparenchymal
hemorrhages, 303 ischemic strokes (264 thrombotic and 39 embolic
infarctions), and 90 strokes of undetermined type. Among thrombotic
infarctions, 90 large-artery occlusive infarctions and 142 lacunar
infarctions were identified. Compared with women who ate fish
less than once per month, those with higher intake of fish had a
lower risk of total stroke: the multivariate relative risks
(RRs), adjusted for age, smoking, and other cardiovascular risk
factors, were 0.93 (95% confidence interval [CI], 0.65-1.34) for
fish consumption 1 to 3 times per month, 0.78 (95% CI, 0.55-1.12)
for once per week, 0.73 (95% CI, 0.47-1.14) for 2 to 4 times per
week, and 0.48 (95% CI, 0.21-1.06) for 5 or more times per week
(P for trend =.06). Among stroke subtypes, a significantly reduced
risk of thrombotic infarction was found among women who ate fish
2 or more times per week (multivariate RR, 0.49; 95% CI, 0.26-0.93).
Women in the highest quintile of intake of long-chain omega-3 polyunsaturated
fatty acids had reduced risk of total stroke and thrombotic infarction,
with multivariate RRs of 0.72 (95% CI, 0.53-0.99) and 0.67 (95%
CI, 0.42-1.07), respectively. When stratified by aspirin use,
fish and omega-3 polyunsaturated fatty acid intakes were inversely
associated with risk of thrombotic infarction, primarily among women
who did not regularly take aspirin. There was no association
between fish or omega-3 polyunsaturated fatty acid intake and risk
of hemorrhagic stroke. CONCLUSIONS: Our data indicate that higher
consumption of fish and omega-3 polyunsaturated fatty acids is associated
with a reduced risk of thrombotic infarction, primarily among
women who do not take aspirin regularly, but is not related to risk
of hemorrhagic stroke. |
Clinical
trial evidence for the cardioprotective effects of omega-3 fatty
acids.
Harris WS: Mid America Heart Institute of Saint Luke's Hospital
and Department of Medicine, University of Missouri-Kansas City,
USA; Isley WL
Curr Atheroscler Rep 2001 Mar 3:174-9
Abstract
The notion that marine omega (w)-3 fatty acids might have beneficial
cardiovascular effects was first suggested by epidemiologic studies
in Greenland Inuits published in the late 1970s. These simple
observations spawned hundreds of other studies, the confluence
of which strongly suggests a true cardioprotective effect of w-3
fatty acids. The strongest confirmation has come from the publication
of three randomized clinical trials, all of which reported benefits
to patients with preexisting coronary artery disease. The most
convincing of these was the Gruppo Italiano per lo Studio della
Sopravvivenza nell'Infarto miocardico (GISSI)-Prevezione study,
in which 5654 patients with coronary artery disease were randomized
to either w-3 fatty acids (850 mg/d) or usual care. After 3.5
years, those taking the w-3 fatty acids had experienced a 20%
reduction in overall mortality and a 45% decrease in risk for
sudden cardiac death. These findings support the view that relatively
small intakes of w-3 fatty acids are indeed cardioprotective,
and suggest that they may operate by stabilizing the myocardium
itself.
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Fish consumption
and the 30-year risk of fatal myocardial infarction.
Daviglus ML: Department of Preventive Medicine, Northwestern University
Medical School, Chicago IL, USA; Stamler J, Orencia AJ, Dyer AR,
Liu K, Greenland P, Walsh MK, Morris D, Shekelle RB
N Engl J Med 1997 Apr 336:1046-53
Abstract
BACKGROUND: Epidemiologic data on the possible benefit of eating
fish to reduce the risk of coronary heart disease have been inconsistent.
We used data from the Chicago Western Electric Study to examine
the relation between base-line fish consumption and the 30-year
risk of death from coronary heart disease. METHODS: The study
participants were 1822 men who were 40 to 55 years old and free
of cardiovascular disease at base line. Fish consumption, as
determined from a detailed dietary history, was stratified (0, 1
to 17, 18 to 34, and > or = 35 g per day). Mortality from coronary
heart disease, ascertained from death certificates, was classified
as death from myocardial infarction (sudden or nonsudden) or death
from other coronary causes. RESULTS: During 47,153 person-years
of follow-up, there were 430 deaths from coronary heart disease;
293 were due to myocardial infarctions (196 were sudden, 94 were
nonsudden, and 3 were not classifiable). Cox proportional-hazards
regression showed that for men who consumed 35 g or more of fish
daily as compared with those who consumed none, the relative risks
of death from coronary heart disease and from sudden or nonsudden
myocardial infarction were 0.62 (95 percent confidence interval,
0.40 to 0.94) and 0.56 (95 percent confidence interval, 0.33 to
0.93), respectively, with a graded relation between the relative
risks and the strata of fish consumption (P for trend = 0.04
and 0.02, respectively). These findings were accounted for by the
relation of fish consumption to nonsudden death from myocardial
infarction (relative risk, 0.33; 95 percent confidence interval,
0.12 to 0.91; P for trend= 0.007). CONCLUSIONS: These data show
an inverse association between fish consumption and death from coronary
heart disease, especially nonsudden death from myocardial infarction.
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