Oméga-3:
faits - thérapeutique et posologie
Diabète:
2,85g - 8,1g/jour EPA et DHA n'ont apporté aucun succès
thérapeutique significatif outre les effets associés
positifs.
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 du diabète.
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Eicosanoid
precursors: potential factors for atherogenesis in diabetic CAPD
patients?
Holler C: Ludwig Boltzmann Institute
for Nutrition, City Hospital Lainz, Vienna, Austria; Auinger M,
Ulberth F, Irsigler K
Perit Dial Int 1996 16 Suppl 1:S250-3
Abstract
Prostaglandins, thromboxanes, and other eicosanoids represent
a widespread lipid-mediator system for intercellular signalling,
and, hence, have multiple cellular actions. Thus it is not surprising
that numerous events in the pathogenesis of atherosclerosis are
associated with an altered formation of eicosanoids. To reconsider
the availability of eiconsanoid precursors as one possible cause
of atherogenesis, the dietary intake and the serum concentrations
of arachidonic acid (AA) and eicosapentaenoic acid (EPA) were
determined in patients with high risk for atherosclerosis on continuous
ambulatory peritoneal dialysis (CAPD) with and without diabetes
in comparison to healthy controls and diabetic patients without
late complications. The factor AA/EPA in serum was created as
a marker for the atherosclerosis risk. The setting was in a CAPD
unit in one city hospital. There were 26 CAPD patients [9 with
insulin-dependent diabetes mellitus (IDDM), 9 with noninsulin-dependent
diabetes mellitus (NIDDM), and 8 without diabetes], 27 IDDM
without late complications, and 41 healthy control persons. The
AA levels in serum were significantly higher in all of the CAPD
groups. In contrast, the EPA concentrations in serum were significantly
lower in the CAPD groups, with the lowest EPA levels found in
the CAPD-IDDM group. Therefore, the factors AA/EPA in serum were
significantly higher in all of the CAPD groups, and again
significantly higher in the CAPD-IDDM group than in the other
CAPD groups. No differences in the amount of dietary intake of
AA existed between the groups. The daily intake of EPA was significantly
highest in the control group. Higher concentrations of AA and
a lack of n-3 fatty acids lead in the presence of a reduced prostaglandin
I2 biosynthesis, to a higher formation rate of potentially proatherogenic
metabolites such as thromboxane A2, a vasoconstricting and platelet
aggregating agent. Thus, the quotient AA/EPA could possibly be
used as a marker of atherogenicity in the future.
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Supplementation
with long-chain n-3 fatty acids in non-insulin-dependent diabetes
mellitus (NIDDM) patients leads to the lowering of oleic acid
content in serum phospholipids.
Haban P: Institute of Preventive and
Clinical Medicine, Bratislava, Slovakia; Zidekova E, Klvanova J
Eur J Nutr 2000 Oct 39:201-6
Abstract
BACKGROUND: The dietary supplementation with EPA (eicosapentaenoic
acid; 20:5n3) and DHA (docosahexaenoic acid; 22:6n3) has been
recommended because of their favourable effects on the cardiovascular
system (including complications of NIDDM). Oleic acid (18:1n9)
from olive oil has some analogous and complementary effects. Potential
competitive relations between long-chain n-3 fatty acids (FAs)
and the oleic acid would therefore mean a problem. AIM OF THE
STUDY: We focused primarily on the oleic acid changes in serum
phospholipids (SPL) after a supplementation with EPA and DHA.
METHODS: Thirty-five patients with type 2 diabetes mellitus
(NIDDM) were supplemented for 28 days with 1.7 g of EPA
plus 1.15 g of DHA/day (as Maxepa capsules, Seven Seas, U.
K.). After that, a 3-month wash-out control period with 21 patients
followed. A fatty acid composition of serum phospholipids (SPL)
was determined by capillary gas-chromatography. Values were calculated
as relative percentages of all FAs. RESULTS: After the supplementation
with the Maxepa capsules, there was a very strong increase in
EPA, docosapentaenoic acid (22:5n3) and DHA content in SPL. It
was followed by a strong decrease after the wash-out (all p <
0.0001). The oleic acid SPL content after the intervention significantly
decreased from 10. 105 +/- 0.307% (mean +/- S. E. M.) to 9.082
+/- 0.276 % (p < 0.0003). During the wash-out, the change was
in the opposite direction (p < 0.0001). When the intervention
and the wash-out periods were taken together, changes in the oleic
acid were inversely correlated with changes in EPA, docosapentaenoic
acid and DHA (r = -0.729; r = -0.552; r = -0.629, respectively;
p < 0.0001; n = 56). On the background of the overall n-6 FA
reduction, the decline in the arachidonic acid after the supplementation
(p < 0.0001) and its rise after the wash-out (p < 0.0003)
were similar. There were no significant changes in the saturated
FA spectrum. CONCLUSIONS: Supplementation with long-chain n-3
FAs in NIDDM patients leads to the lowering of oleic acid SPL
content. Whereas the reduction of the arachidonic acid may
have some desirable aspects (e. g. suppression of thromboxane
TxA2 or 4 series leukotriene production), the decline of the former
is to be regarded as a potential problem. Therefore, the search
for optimally balanced blends of n-3 polyunsaturated fatty acids
(PUFAs) and monounsaturated fatty acids (MUFAs) seems to be more
promising than a supplementation with only one type of FA.
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Effects
of purified eicosapentaenoic and docosahexaenoic acids on glycemic
control, blood pressure, and serum lipids in type 2 diabetic patients
with treated hypertension.
Woodman RJ: Department of Medicine,
The University of Western Australia, Perth, Australia; Mori TA,
Burke V, Puddey IB, Watts GF, Beilin LJ
Am J Clin Nutr 2002 Nov 76:1007-15
Abstract
BACKGROUND: n-3 Fatty acids lower blood pressure, improve
lipids, and benefit other cardiovascular disease risk factors.
Effects on glycemia in patients with type 2 diabetes are uncertain.
OBJECTIVE: We determined whether purified eicosapentaenoic acid
(EPA) and docosahexaenoic acid (DHA) have differential effects
on glycemic control, including insulin sensitivity and stimulated
insulin secretion; 24-h ambulatory blood pressure; and serum lipids
in type 2 diabetic patients with treated hypertension. DESIGN:
In a double-blind, placebo-controlled trial of parallel design,
59 subjects were randomly assigned to consume
4 g EPA, DHA, or olive oil/d for
6 wk while continuing to consume their usual diet.
RESULTS: Thirty-nine men and 12 postmenopausal
women with a mean (+/- SE) age of 61.2 +/- 1.2 y completed the
study. In comparison with the change from baseline
in fasting glucose in the olive oil group, fasting glucose in
the EPA and DHA groups increased 1.40 +/- 0.29 mmol/L (P = 0.002)
and 0.98 +/- 0.29 mmol/L (P = 0.002), respectively. Neither
EPA nor DHA had significant effects on glycated hemoglobin, fasting
insulin or C-peptide, insulin sensitivity or secretion, or blood
pressure. Serum triacylglycerols in the EPA and DHA
groups decreased 19% (P = 0.022) and 15% (P = 0.022), respectively.
There were no significant changes in serum total, LDL, or HDL
cholesterol, although HDL(2) cholesterol in the EPA and DHA groups
increased 16% (P = 0.026) and 12% (P = 0.05), respectively. HDL(3)
cholesterol decreased 11% (P = 0.026) with EPA supplementation.
CONCLUSIONS: EPA and DHA had similar
benefits on lipids but adverse effects on short-term glycemic
control in hypertensive diabetic patients. The overall
implications for cardiovascular disease require long-term evaluation.
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Plasmatic
factors of haemostasis remain essentially unchanged except for PAI
activity during n-3 fatty acid intake in type I diabetes mellitus.
Spannagl M: Klinikum Innenstadt, Ludwig-Maximilians-Universität
München, Germany; Drummer C, Fröschl H, von
Schacky C, Landgraf-Leurs MM, Landgraf R, Schramm W
Blood Coagul Fibrinolysis 1991 Apr 2:259-65
Abstract
Diabetic patients are prone to develop vascular
complications. Increased procoagulatory factors and a reduced fibrinolytic
potential are considered as thrombogenic risk factors, although
controversy remains. In epidemiological and dietary intervention
studies fish or fish oil, rich in the two n-3 fatty acids eicosapentaenoic
acid (EPA) and docosahexaenoic acid (DHA), have demonstrated a potential
to reduce cardiovascular disease. We compared the plasmatic coagulatory
and fibrinolytic profile of 13 near normoglycaemic
type I diabetics almost free of cardiovascular disease
with healthy volunteers, matched for age and sex. Except for fibrinogen
levels and the activity being elevated and soluble fibrin and fibrinopeptide
A being reduced, no differences could be discerned between type
I diabetics and controls in all investigated plasmatic parameters.
In a dietary intervention study we investigated
the effects of 5.4 g EPA and 2.7 g DHA per day during and after
a 4-week dietary supplementation in the diabetic patients.
The factors, inhibitors and activation products of coagulation and
fibrinolysis measured were at best transiently affected by the diet.
Only plasminogen activator inhibitory activity PAI in plasma significantly
increased during the dietary supplementation and returned to prediet
values after cessation of n-3 fatty acids. Changes in PAI activity
were negatively correlated to changes in serum triglycerides. We
conclude that well adjusted type I diabetics show an almost unchanged
haemostatic profile compared to matched healthy controls. A
dietary intervention with n-3 fatty acids in these patients does
not affect the plasmatic haemostatic pattern except for an increase
in PAI activity. |
The
effect of n-3 fatty acid administration on selected indicators of
cardiovascular disease risk in patients with type 2 diabetes mellitus.
Habán P: Klinické oddelenie
Výskumného ústavu výzivy v Bratislave;
Simoncic R, Klvanová I, Ozdín L, Zideková E
Bratisl Lek Listy 1998 Jan 99:37-42
Abstract
BACKGROUND: Serum triacylglycerols (TG), VLDL, HDL, fatty
acid and eicosanoid spectrum are among the factors determining the
risk of cardiovascular complications in NIDDM. N-3 polyunsaturated
fatty acids (PUFA) are expected to have beneficial effects on these
factors. In NIDDM patients there have however been previously reported
(late 1980s) some adverse effects. OBJECTIVES: Our aim was to verify
the effects of n-3 PUFA in NIDDM patients using relatively low dosage.
METHODS: The investigated group included 21
NIDDM patients with dyslipoproteinemia type IV. The patients were
treated for 28 days with 1.7 g EPA (eicosapentaenoic acid) + 1.15
g DHA (docosahexaenoic acid)/day (10 capsules/day of
MAXEPA, Seven Seas U.K.). The lipoproteins were measured using the
BIO-LACHEMA kits, the fatty acid spectrum in phospholipids was determined
by gas chromatography and prostanoids (after their separation) were
measured by RIA methods. MAIN RESULTS AND CONCLUSIONS: After the
MAXEPA treatment there has been a strong
decrease in TG (p < 0.005) and VLDL (p < 0.002) serum levels,
accompanied by a significant increase in HDL (p < 0.02).
The final-to-baseline TG ratio in individual patients negatively
correlated with the relative percentage of EPA in phospholipids
after the treatment (p < 0.03; r = -0.474).
There was no significant change in serum total cholesterol, fasting
glycaemia and glycosylated hemoglobin. There was a slight,
but statistically already significant (p < 0.05), rise in LDL.
The relative percentage of EPA, docosapentaenoic acid and DHA in
serum phospholipids increased sharply (p < 0.001, p < 0.001,
p < 0.001). The increase of n-3 PUFA
in individual patients was linked with the decrease in n-6 PUFA
(p < 0.001; r = -0.686). The spectrum of the latter
has changed also very markedly. The prostacyclin PGI2-to-thromboxane
TxA2 ratio increased significantly (p < 0.001).
Beneficial effects of n-3 fatty acids have prevailed and this kind
of treatment seems very encouraging also in NIDDM patients.
The results are logically compatible with other authors' results
pattern formed in 1990s. A slight rise in serum LDL needs a more
detailed discussion since only its phenotype B ("small dense LDL
particles") has been recently found to be atherogenic. |
Long-term
administration of highly purified eicosapentaenoic acid ethyl ester
prevents diabetes and abnormalities of blood coagulation in male
WBN/Kob rats.
Nobukata H: Toxicology Laboratory, Research
Center, Mochida Pharmaceutical, Shizuoka, Japan; Ishikawa T,
Obata M, Shibutani Y
Metabolism 2000 Jul 49:912-9
Abstract
We investigated the effect of long-term administration
of highly purified eicosapentaenoic acid ethyl ester (EPA-E), an
n-3 polyunsaturated fatty acid, on the development of diabetes,
insulin resistance, and abnormalities of blood coagulation in male
WBN/Kob rats, a model of spontaneous diabetes mellitus. After 8-month
oral EPA-E treatment, the incidence of diabetes at a dose of 0.1,
0.3, and 1.0 g/kg was 92%, 50%, and 17%, respectively. Its incidence
was suppressed significantly and dose-dependently at a dose of 0.3
g/kg or higher compared with the rate (100%) for the vehicle control.
Additionally, EPA-E significantly and dose-dependently decreased
the elevation of plasma glucose after an oral glucose load and increased
the glucose infusion rate (GIR) during the euglycemic insulin-glucose
clamp test at a dose of 0.1 g/kg or higher compared with the vehicle
control. Furthermore, EPA-E significantly and dose-dependently
ameliorated coagulation-related parameters, including the prothrombin
time (PT), activated partial thromboplastin time (APTT), fibrinogen
level, and factor II, V, VII, VIII, IX, X, XI, and XII and antithrombin
III (AT III) activities, and fibrinolysis-related parameters, including
plasminogen, tissue-type plasminogen activator (t-PA), alpha2-plasmin
inhibitor (alpha2-PI), and plasminogen activator inhibitor (PAI),
and also suppressed ADP- or collagen-induced platelet aggregation
and the cholesterol to phospholipid (C/P) molar ratio in platelet
membranes at a dose of 0.1 g/kg or higher. These data demonstrate
multiple actions of the product in these laboratory animals. These
include changes in platelet function, coagulation/fibrinolysis factors,
plasma immunoreactive insulin secretion, and plasma glucose/insulin
resistance. |
Health
benefits of docosahexaenoic acid (DHA)
Horrocks LA: Docosa Foods Ltd, 1275
Kinnear Road, 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. |
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