Beneficial
Effects on the Immune System
Flaxseed contains two components that favourably affect the
immune system: alpha-linolenic acid (ALA), an essential omega-3
fatty acid, and lignans, a type of phytoestrogen. These components
affect immune cells and mediators of the immune response such
as eicosanoids and cytokines. ALA, for example, suppresses
the proliferation of peripheral blood mononuclear lymphocytes
and the delayed hypersensitivity response to certain antigens.1 Recent
research suggests that ALA and lignans in flaxseed modulate
the immune response and may play a beneficial role in the clinical
management of autoimmune diseases.2, 3
Flaxseed Effects on the Immune
System
The ALA component of flaxseed
influences immunity - the body's ability to defend itself successfully
against foreign substances - through its effects on membrane
phospholipids and the production of eicosanoids and cytokines.
Lignans influence certain mediators of the immune response.
Membrane Phospholipids
ALA and other omega-3 fatty
acids influence the immune response by altering the fatty acid
composition of membrane phospholipids, which in turn significantly
affects eicosanoid production. ALA in flaxseed increases phospholipid
ALA, EPA and DHA levels in mononuclear cells,4 neutrophils,5 lipoproteins,5,
6 and platelets.7 This change in membrane phospholipid
content results in reduced biosynthesis of arachidonic acid from
linoleic acid and decreased production of the proinflammatory
eicosanoids, leukotriene B4 (LTB4) and
thromboxane A2 (TXA2),8, 9 shown in Figure 1. Increasing
the ALA and omega-3 fatty acid content of membrane phospholipids
enhances the biosynthesis of postgladin I3 (PGI3)
and other eicosanoids of the
3- and 5-series that
are less inflammatory.10
Eicosanoid Production
Eicosanoids are a
group of biologically active compounds derived from polyunsaturated
fatty acids such as arachidonic acid.9 In rats,
mice and cynomolgus monkeys, ALA suppresses tissue levels of
arachidonic acid and the biosynthesis of eicosanoids, but not
to the same extent as EPA and DHA.8, 11, 12 In humans,
prostaglandin biosynthesis is also influenced by ALA intake.
In one study, six healthy women consumed isocaloric formula
diets providing a constant amount of linoleic acid and different
amounts of ALA (0%, 4% and 8% of total energy); each formula
diet was consumed for two weeks. Total prostaglandin biosynthesis
decreased nearly 50% at the highest ALA intake level.13 In
a study of a single male subject, the urinary excretion
of metabolites of TXA2 and PGI2 decreased 34% during the seven week period in which
the subject consumed a mix of flaxseed and canola oils.14. In another
study, PGE2 and thromboxane B2 production was inhibited significantly when
subjects (28 healthy men) consumed a flaxseed oil-based diet for
eight weeks.4
1 Some
intermediate compounds in the omega-3 and omega-6 fatty acid
pathways are not shown.
2 Abbreviations: DGLA, dihomo-gamma-linolenic acid; DHA,
docosahexaenoic acid; EPA, eicosapentaenoic
acid; PGE1, prostaglandin
E1; PGI3, prostaglandin I3;
LTB4, leukotriene B4; TXA2,
thromboxane A2.
3 Other
eicosanoids derived from DGLA include other members of the 1-series
prostanoids (prostaglandins and thromboxanes) and the 3-series
leukotrienes.
4 Other
eicosanoids derived from EPA include other members of the 3-series
prostanoids (prostaglandins and thromboxanes) and the 5-series
leukotrienes.
5 Other
eicosanoids derived from arachidonic acid include other members
of the 2-series prostanoids (prostaglandins and thromboxanes)
and the 4-series leukotrienes.
Cytokine Production
Cytokines are soluble proteins liberated from immune
cells in response to injury, infection or exposure to foreign
substances.15 Two cytokines that contribute to
inflammation are tumour necrosis factor (TNF) and interleukin-1
(IL-1). Both are present in rheumatoid joints and contribute
to the tissue pathology of rheumatoid arthritis;16 and
they stimulate the release of platelet-activating factor,
a potent mediator of inflammation.3 The production
of TNF and IL-1 by macrophages is influenced by dietary ALA
and the ALA to linoleic acid ratio.17 Consumption
of a flaxseed-oil based diet for eight weeks, for example,
resulted in an inhibition of TNF and IL-1 b production of
about 77-81% in a study of 28 healthy men.4 Several
studies have demonstrated significant reductions in TNF and
IL-1 levels in humans consuming omega-3 fatty acids.18
Potential Uses of
Flaxseed in Clinical Medicine
Flaxseed may prove useful in the nutritional
management of patients with autoimmune diseases. For example,
systemic lupus erythematosus (SLE) is an inflammatory disease
that occurs mainly in young women. It is characterized by a
variety of clinical findings, including inflammation of the
kidney (nephritis). Studies show that patients with SLE exhibit
increased production of platelet-activating factor (PAF), a
mediator of immune response and promoter of platelet aggregation.19 Dietary
flaxseed has provided significant benefits in animal models
of lupus nephritis and in patients with this condition.3 In
one study of nine patients with lupus nephritis, PAF-induced
platelet aggregation was inhibited and renal function improved
when subjects consumed 15 to 45 g flaxseed/day for four weeks.20 The
lignan component of flaxseed is believed to be responsible
for this effect.21
Flaxseed Has Favourable
Effects on the Immune System
Flaxseed favourably
influences immune response. The flaxseed component, ALA, alters
membrane phospholipids, inhibits arachidonic acid biosynthesis
from linoleic acid, inhibits the production of proinflammatory
eicosanoids from arachidonic acid, and suppresses lymphocyte
proliferation and cytokine production.22, 23 Flaxseed
lignans are potent inhibitors of platelet-activating factor,
a mediator of inflammation.3 Through these effects,
flaxseed has the potential to be used for the treatment of disorders
characterized in part by activated lymphocytes and a hyper-stimulated
immune response. Such disorders include rheumatoid arthritis,
psoriasis, multiple sclerosis and systemic lupus erythematosus.3,
24
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Flax Council of Canada, 465-167 Lombard Ave., Winnipeg, MB, Canada R3B
0T6, email: flax@flaxcouncil.ca,
Web site: http://www.flaxcouncil.ca/
