Oméga-3:
faits - thérapeutique et posologie
Pour
la dépression, il n'existe encore aucune
valeur de référence thérapeutique.
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 la dépression.
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Omega-3
polyunsaturated fatty acid levels in the diet and in red blood
cell membranes of depressed patients.
Edwards R: University Department of Psychiatry, University
of Sheffield, UK; Peet M, Shay J, Horrobin D
J Affect Disord 1998 Mar 48:149-55
Abstract
BACKGROUND: There is a hypothesis that lack of n-3 polyunsaturated
fatty acids (PUFAs) is of aetiological importance in depression.
Docosahexaenoic acid, a member of the n-3 PUFA family, is a crucial
component of synaptic cell membranes. The aim of this study was
to measure RBC membrane fatty acids in a group of depressed patients
relative to a well matched healthy control group. METHOD: Red
blood cell (RBC) membrane levels, and dietary PUFA intake were
measured in 10 depressed patients and 14 matched healthy control
subjects. RESULTS: There was a significant depletion of RBC
membrane n-3 PUFAs in the depressed subjects which was not due
to reduced calorie intake. Severity of depression correlated negatively
with RBC membrane levels and with dietary intake of n-3 PUFAs.
CONCLUSION: Lower RBC membrane n-3 PUFAs are associated with the
severity of depression. LIMITATIONS: Although patient numbers
were small, confounding factors were well controlled for and the
results were highly significant. Results of the dietary data would
tend to be weakened due to the limitations associated with dietary
assessment. CLINICAL RELEVANCE: The findings raise the possibility
that depressive symptoms may be alleviated by n-3 PUFA supplementation.
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Arachidonic
acid to eicosapentaenoic acid ratio in blood correlates positively
with clinical symptoms of depression.
Adams PB: Central Region Mental Health
Service, Rockhampton Base Hospital, Queensland, Australia; Lawson S,
Sanigorski A, Sinclair AJ
Lipids 1996 Mar 31 Suppl:S157-61
Abstract
In this study of 20 moderately to severely depressed
patients, diagnosed using current research diagnostic criteria
and excluding known bipolar affective disorder and reactive depression,
we investigated relationships between severity of depression and
levels and ratios of n-3 and n-6 long-chain polyunsaturated fatty
acids (PUFA) in plasma and erythrocyte phospholipids (PL). Severity
of depression was measured using the 21-item Hamilton depression
rating scale (HRS) and a second linear rating scale (LRS) of severity
of depressive symptoms that omitted anxiety symptoms. There
was a significant correlation between the ratio of erythrocyte
PL arachidonic acid (AA) to eicosapentaenoic acid (EPA) and severity
of depression as rated by the HRS (P < 0.05) and the LRS for
depression (P < 0.01). There was also a significant negative
correlation between erythrocyte EPA and the LRS (P < 0.05).
The AA/EPA ratio in plasma PL and the ratio of erythrocyte long-chain
(C20 and C22 carbon) n-6 to long-chain n-3 PUFA were also significantly
correlated with the LRS (P < 0.05). These findings do not
appear to be simply explained by differences in dietary intake
of EPA. We cannot determine whether the high ratios of AA/EPA
in both plasma and erythrocyte PL are the result of depression
or whether tissue PUFA change predate the depressive symptoms.
We suggest, however, that our findings provide a basis for studying
the effect of the nutritional supplementation of depressed subjects,
aimed at reducing the AA/EPA ratio in tissues and severity of
depression.
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Depletion
of omega-3 fatty acid levels in red blood cell membranes of depressive
patients.
Peet M: University Department of Psychiatry,
Sheffield, United Kingdom; , Murphy B, Shay J, Horrobin D
Biol Psychiatry 1998 Mar 43:315-9
Abstract
BACKGROUND: It has been hypothesized that depletion of
cell membrane n3 polyunsaturated fatty acids (PUFA), particularly
docosahexanoic acid (DHA), may be of etiological importance in
depression. METHODS: We measured the fatty acid composition of
phospholipid in cell membranes from red blood cells (RBC) of 15
depressive patients and 15 healthy control subjects. RESULTS:
Depressive patients showed significant depletions of total
n3 PUFA and particularly DHA. Incubation of RBC from control
subjects with hydrogen peroxide abolished all significant differences
between patients and controls. CONCLUSIONS: These findings suggest
that RBC membranes in depressive patients show evidence of oxidative
damage. Possible interpretations, and implications for the etiology
and treatment of depression, are discussed.
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Omega 3
fatty acids in bipolar disorder: a preliminary double-blind, placebo-controlled
trial.
Stoll AL, Severus WE, Freeman MP, Rueter S, Zboyan HA, Diamond E,
Cress KK, Marangell LB
Arch Gen Psychiatry 1999 May 56:407-12
Abstract
BACKGROUND: Omega3 fatty acids may inhibit neuronal signal transduction
pathways in a manner similar to that of lithium carbonate and valproate,
2 effective treatments for bipolar disorder. The present study was
performed to examine whether omega3 fatty acids also exhibit mood-stabilizing
properties in bipolar disorder. METHODS: A 4-month,
double-blind, placebo-controlled study, comparing omega3
fatty acids (9.6 g/d) vs placebo (olive oil), in addition
to usual treatment, in 30 patients with
bipolar disorder. RESULTS: A Kaplan-Meier survival analysis
of the cohort found that the omega3 fatty
acid patient group had a significantly longer period of remission
than the placebo group (P = .002; Mantel-Cox). In addition,
for nearly every other outcome measure, the
omega3 fatty acid group performed better than the placebo group.
CONCLUSION: Omega3 fatty acids were well tolerated and improved
the short-term course of illness in this preliminary study of patients
with bipolar disorder. |
Seafood
consumption, the DHA content of mothers' milk and prevalence rates
of postpartum depression: a cross-national, ecological analysis.
Hibbeln JR: Laboratory of Membrane Biophysics
and Biochemistry, National Institute on Alcohol Abuse and Alcoholism,
National Institutes of Health, Park 5, Room 150, 12420 Parklawn
Drive, Rockville, MD 20892, USA
J Affect Disord 2002 May 69:15-29
Abstract
BACKGROUND: Mothers selectively transfer docosahexaenoic
acid (DHA) to their fetuses to support optimal neurological development
during pregnancy. Without sufficient dietary intake, mothers
become depleted of DHA and may increase their risk of suffering
major depressive symptoms in the postpartum period. We postulated
that the DHA content of mothers' milk and seafood consumption would
both predict prevalence rates of postpartum depression across countries.
METHODS: Published prevalence data for postpartum depression were
included that used the Edinburgh Postpartum Depression Scale (n=14532
subjects in 41 studies). These data were compared to the DHA, eicosapentaenoic
acid (EPA) and arachidonic acid (AA) content in mothers' milk and
to seafood consumption rates in published reports from 23 countries.
RESULTS: Higher concentrations of DHA in mothers' milk (r=-0.84,
p<0.0001, n=16 countries) and greater seafood consumption (r=-0.81,
p<0.0001, n=22 countries) both predicted lower prevalence rates
of postpartum depression in simple and logarithmic models, respectively.
The AA and EPA content of mothers' milk were unrelated to postpartum
depression prevalence. LIMITATIONS: These findings do not prove
that higher omega-3 status cause lower prevalence rates of postpartum
depression. Data on potentially confounding factors were not uniformly
available for all countries. CONCLUSIONS: Both lower DHA content
in mothers' milk and lower seafood consumption were associated with
higher rates of postpartum depression. These results do not
appear to be an artifact of cross-national differences in well-established
risk factors for postpartum depression. Interventional studies are
needed to determine if omega-3 fatty acids can reduce major postpartum
depressive symptoms. |
A
replication study of violent and nonviolent subjects: cerebrospinal
fluid metabolites of serotonin and dopamine are predicted by plasma
essential fatty acids.
Hibbeln JR: Laboratory of Membrane Biochemistry
and Biophysics, National Institute on Alcohol Abuse and Alcoholism,
Bethesda, Maryland, USA; Umhau JC, Linnoila M, George DT,
Ragan PW, Shoaf SE, Vaughan MR, Rawlings R,
Salem N
Biol Psychiatry 1998 Aug 44:243-9
Abstract
BACKGROUND: Among an independent group of
subjects selected for their history of violent, impulsive behaviors
and nonviolent control subjects, we attempted to replicate the finding
that plasma docosahexaenoic acid concentrations were negatively
correlated with cerebrospinal fluid 5-hydroxyindoleacetic acid (CSF
5-HIAA) concentrations. METHODS: CSF 5-HIAA and homovanillic acid
(HVA), fasting total cholesterol, and plasma fatty acid concentrations
were examined in violent and nonviolent subjects matched for their
severity of alcohol dependence. RESULTS: Violent subjects had significantly
higher lifetime violence and hostility ratings and lower concentrations
of CSF 5-HIAA than nonviolent subjects. Plasma docosahexaenoic acid
was negatively correlated with CSF 5-HIAA only among violent subjects.
CONCLUSIONS: This observational study suggests that dietary essential
fatty acids may change neurotransmitter concentrations. Prospective
dietary intervention trials will be required to determine if increasing
dietary intake of docosahexaenoic acid will increase or decrease
either CSF 5-HIAA concentrations or impulsive and violent behaviors.
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A
placebo-controlled trial of omega-3 fatty acid (ethyl eicosapentaenoic
acid) supplementation for residual symptoms and cognitive impairment
in schizophrenia.
Fenton WS: NIMH, NIH, Bethesda, MD 20892-9621,
USA; Dickerson F, Boronow J, Hibbeln JR, Knable M
Am J Psychiatry 2001 Dec 158:2071-4
Abstract
OBJECTIVE: This study determined if augmentation of neuroleptics
with 3 g/day of ethyl eicosapentaenoic acid (EPA) improves symptoms
and cognition in patients with schizophrenia or schizoaffective
disorder. METHOD: Eighty-seven patients meeting criteria for schizophrenia
or schizoaffective disorder who had residual symptoms despite neuroleptic
treatment were randomly assigned to receive either 3 g/day of ethyl
EPA (N=43) or placebo (N=44) in a 16-week, double-blind supplementation
trial. Assessments were performed at baseline and at weeks 1, 2,
4, 8, 12, and 16; a cognitive battery was administered at baseline
and at week 16. RESULTS: No differences were found between groups
in positive or negative symptoms, mood, cognition, or global impression
ratings. Results were similar for the intention-to-treat (N=87)
and completer (N=75) groups. CONCLUSIONS: For schizophrenia patients
treated with 3 g/day of ethyl EPA, improvement in residual symptoms
and cognitive impairment was no greater than for schizophrenia patients
treated with placebo. |
Fish
consumption and depressive symptoms in the general population in
Finland.
Tanskanen A: Department of Psychiatry,
University of Kuopio, Finland; Hibbeln JR, Tuomilehto J,
Uutela A, Haukkala A, Viinamäki H, Lehtonen J,
Vartiainen E
Psychiatr Serv 2001 Apr 52:529-31
Abstract
Fish contains high concentrations of omega-3 polyunsaturated
fatty acids. Several studies have reported depletions of omega-3
fats among depressed patients, and a cross-national comparison has
revealed a significant inverse correlation between annual prevalence
of major depression and fish consumption. In a sample of 3,204
Finnish adults, depressive symptoms were estimated with the Beck
Depression Inventory. A frequency question was used to measure
fish consumption. Multiple logistic regression analysis was conducted
to assess the association between depression and fish consumption.
After the analysis adjusted for potential confounders, the likelihood
of having depressive symptoms was significantly higher among infrequent
fish consumers than among frequent consumers. |
Plasma
total cholesterol concentrations do not predict cerebrospinal fluid
neurotransmitter metabolites: implications for the biophysical role
of highly unsaturated fatty acids.
Hibbeln JR: Laboratories of Membrane
Biochemistry and Biophysics and Clinical Studies, National Institute
on Alcohol Abuse and Alcoholism, Bethesda, MD 20852, USA; Umhau JC,
George DT, Shoaf SE, Linnoila M, Salem N
Am J Clin Nutr 2000 Jan 71:331S-8S
Abstract
Low concentrations of a metabolite of serotonin found in
cerebrospinal fluid (CSF), 5-hydroxyindolacetic acid (5-HIAA), are
strongly associated with suicidal and violent behaviors. Although
lowering of plasma total cholesterol has been suggested to increase
mortality from suicide and violence by decreasing concentrations
of CSF 5-HIAA via changes in membrane biophysical properties, highly
unsaturated fatty acids may play a more important role. Violent
and nonviolent comparison groups, early- and late-onset alcoholics,
and healthy comparison subjects were studied to control for alcohol
use and predisposition to violence. Fasting plasma total cholesterol
and CSF were assayed under stringently controlled conditions. When
all groups were combined (n = 234), plasma cholesterol concentrations
had a weak positive correlation with CSF 5-HIAA (r = 0.18, P <
0.01). However, age correlated with both plasma total cholesterol
and CSF 5-HIAA concentrations. When age was included in multiple
regression models, the correlation between cholesterol and CSF 5-HIAA
concentrations was not significant. Cholesterol correlated weakly
with CSF 5-HIAA concentrations only in late-onset alcoholics after
age was controlled for, but the relation was not significant after
correction for multiple testing. CSF homovanillic acid did not correlate
with plasma total cholesterol in any group. Plasma total cholesterol
had no apparent relation to CSF neurotransmitter metabolites in
any group of subjects. Highly unsaturated essential fatty acids,
which are also critical determinants of membrane biophysical properties
and may be linked to brain serotonin concentrations, should
also be considered in studies examining the effect of lowering fat
intake on the incidence of suicide and violence. |
Fatty acid
composition in major depression: decreased omega 3 fractions in
cholesteryl esters and increased C20: 4 omega 6/C20:5 omega 3 ratio
in cholesteryl esters and phospholipids.
Maes M: Clinical Research Center, University Department of Psychiatry,
Antwerp, Belgium; Smith R, Christophe A, Cosyns P, Desnyder R, Meltzer
H
J Affect Disord 1996 Apr 38:35-46
Abstract
Recently, there were some reports that major depression may be accompanied
by alterations in serum total cholesterol, cholesterol ester and
omega 3 essential fatty acid levels and by an increased C20: 4 omega
6/C20: 5 omega 3, i.e., arachidonic acid/eicosapentaenoic, ratio.
The present study aimed to examine fatty acid composition of serum
cholesteryl esters and phospholipids in 36 major depressed, 14 minor
depressed and 24 normal subjects. Individual saturated (e.g., C14:0;
C16:0, C18:0) and unsaturated (e.g., C18:1, C18:2, C20:4) fatty
acids in phospholipid and cholesteryl ester fractions were assayed
and the sums of the percentages of omega 6 and omega 3, saturated,
branched chain and odd chain fatty acids, monoenes as well as the
ratios omega 6/omega 3 and C20:4 omega 6/C20:5 omega 3 were calculated.
Major depressed subjects had significantly higher C20:4 omega
6/C20:5 omega 3 ratio in both serum cholesteryl esters and phospholipids
and a significantly increased omega 6/omega 3 ratio in cholesteryl
ester fraction than healthy volunteers and minor depressed subjects.
Major depressed subjects had significantly lower C18:3 omega 3 in
cholesteryl esters than normal controls. Major depressed subjects
showed significantly lower total omega 3 polyunsaturated fatty acids
in cholesteryl esters and significantly lower C20:5 omega 3 in serum
cholesteryl esters and phospholipids than minor depressed subjects
and healthy controls. These findings suggest an abnormal intake
or metabolism of essential fatty acids in conjunction with decreased
formation of cholesteryl esters in major depression. |
Fatty acid
analysis of blood plasma of patients with Alzheimer's disease, other
types of dementia, and cognitive impairment.
Conquer JA: Department of Human Biology and Nutritional Sciences,
University of Guelph, Ontario, Canada; Tierney MC, Zecevic J, Bettger
WJ, Fisher RH
Lipids 2000 Dec 35:1305-12
Abstract
Fatty acid differences, including docosahexaenoic acid (DHA; 22:6n-3)
have been shown in the brains of Alzheimer's patients (AD) as compared
with normal age-matched individuals. Furthermore, low serum DHA
is a significant risk factor for the development of AD. The relative
concentration of DHA and other fatty acids, however, in the plasma
of AD patients compared with patients with other kinds of dementias
(other dementias; OD), patients who are cognitively impaired but
nondemented (CIND), or normal patients is not known. In this study
we analyzed the total phospholipid, phosphatidylcholine (PC), phosphatidylethanolamine
(PE), and lysophosphatidylcholine (lysoPC) fractions of plasma from
patients diagnosed with AD, OD, or CIND and compared them with a
group of elderly control subjects with normal cognitive functioning.
Plasma phospholipid and PC levels of 20:5n-3, DHA, total n-3 fatty
acids, and the n-3/n-6 ratio were lower in the AD, OD, and CIND
groups. Plasma phospholipid 24:0 was lower in the AD, OD, and CIND
groups as compared with the group of control patients, and total
n-6 fatty acid levels were higher in the AD and CIND groups only.
In the plasma PE fraction, levels of 20:5n-3, DHA, and the total
n-3 fatty acid levels were significantly lower in the AD, OD, and
CIND groups. DHA levels were lower in the lysoPC fraction of CIND
individuals only. There were no other differences in the fatty acid
compositions of the different phospholipid fractions. Therefore,
in AD, OD, and CIND individuals, low levels of n-3 fatty acids in
the plasma may be a risk factor for cognitive impairment and/or
dementia. Interestingly, a decreased level of plasma DHA was
not limited to the AD patients but appears to be common in cognitive
impairment with aging. |
Two double-blind
placebo-controlled pilot studies of eicosapentaenoic acid in the
treatment of schizophrenia.
Peet M: Academic Department of Psychiatry, Northern General Hospital,
The Longley Centre, Sheffield, UK; Brind J, Ramchand CN, Shah S,
Vankar GK
Schizophr Res 2001 Apr 49:243-51
Abstract
Evidence that the metabolism of phospholipids and polyunsaturated
fatty acids (PUFA) is abnormal in schizophrenia provided the rationale
for intervention studies using PUFA supplementation. An initial
open label study indicating efficacy for n-3 PUFA in schizophrenia
led to two small double-blind pilot studies. The first study was
designed to distinguish between the possible effects of two different
n-3 PUFA: eicosapentaenoic acid (EPA) and docohexaenoic acid (DHA).
Forty-five schizophrenic patients on stable antipsychotic medication
who were still symptomatic were treated with either EPA, DHA or
placebo for 3 months. Improvement on EPA measured by the Positive
and Negative Syndrome Scale (PANSS) was statistically superior to
both DHA and placebo using changes in percentage scores on the total
PANSS. EPA was significantly superior to DHA for positive symptoms
using ANOVA for repeated measures. In the second placebo-controlled
study, EPA was used as a sole treatment, though the use of antipsychotic
drugs was still permitted if this was clinically imperative. By
the end of the study, all 12 patients on placebo, but only eight
out of 14 patients on EPA, were taking antipsychotic drugs. Despite
this, patients taking EPA had significantly lower scores on the
PANSS rating scale by the end of the study. It is concluded that
EPA may represent a new treatment approach to schizophrenia,
and this requires investigation by large-scale placebo-controlled
trials. |
Randomized,
placebo-controlled study of ethyl-eicosapentaenoic acid as supplemental
treatment in schizophrenia.
Emsley R, Myburgh C, Oosthuizen P, van Rensburg SJ
Am J Psychiatry 2002 Sep 159:1596-8
Abstract
OBJECTIVE: The study investigated the efficacy and tolerability
of ethyl-eicosapentaenoic acid (E-EPA) as add-on treatment in chronic,
severe schizophrenia. METHOD: A randomized, parallel-group, double-blind,
placebo-controlled, fixed-dose, add-on study was conducted over
12 weeks. Forty patients with persistent symptoms after at least
6 months of stable antipsychotic treatment received E-EPA or placebo,
in addition to their existing treatment. RESULTS: At 12 weeks, the
E-EPA group had significantly greater reduction of Positive and
Negative Syndrome Scale total scores and of dyskinesia scores than
the placebo group. CONCLUSIONS: EPA may be an effective and well-tolerated
add-on treatment in schizophrenia. |
Addition
of omega-3 fatty acid to maintenance medication treatment for recurrent
unipolar depressive disorder.
Nemets B: Ministry of Health Mental Health Center, Faculty of Health
Sciences, Ben Gurion University of the Negev, Beer-Sheva, Israel;
Stahl Z, Belmaker RH
Am J Psychiatry 2002 Mar 159:477-9
Abstract
OBJECTIVE: Studies have reported that countries with high rates
of fish oil consumption have low rates of depressive disorder. The
authors studied a specific omega-3 fatty acid, the ethyl ester of
eicosapentaenoic acid (E-EPA), as an adjunct to treatment for depressive
episodes occurring in patients with recurrent unipolar depressive
disorder who were receiving maintenance antidepressant therapy.
METHOD: Twenty patients with a current diagnosis of major depressive
disorder participated in a 4-week, parallel-group, double-blind
addition of either placebo or E-EPA to ongoing antidepressant therapy.
Seventeen of the patients were women, and three were men. RESULTS:
Highly significant benefits of the addition of the omega-3 fatty
acid compared with placebo were found by week 3 of treatment.
CONCLUSIONS: It is not possible to distinguish whether E-EPA augments
antidepressant action in the manner of lithium or has independent
antidepressant properties of its own. |
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