Reduces
Inflammatory Responses; Implications for Atherosclerosis
Flaxseed reduces the production of major systemic
markers of inflammatory activity, including eicosanoids,
cytokines and platelet-activating factor. Regular consumption
of flaxseed may influence the progression of atherosclerosis,
an inflammatory disease.
Atherosclerosis is an inflammatory
disease. Its origins are in infancy and childhood when the earliest
lesions, called fatty streaks, begin to develop in arteries.1 Fatty
streaks consist only of monocyte-derived macrophages and T lymphocytes-two
types of immune cells whose presence in arterial walls provides
evidence that the inflammatory response contributes to atherosclerosis.2 Recognizing
the role of inflammation in atherosclerosis suggests a new approach
to cardiovascular disease prevention and treatment: Developing
interventions that alleviate chronic inflammation and may retard
the progression of atherosclerosis.
Flaxseed inhibits the production
of pro-inflammatory cytokines and lipid mediators derived from
arachidonic acid (an omega-6 fatty acid) and thus reduces inflammatory
responses. This effect is likely due to one or both of the following
constituents present in flaxseed: alpha-linolenic acid (ALA),
the essential omega-3 fatty, and lignans, which are phytoestrogens
that exhibit antioxidant, antimitotic and antifungal activity.3 With
its unique fatty acid profile, flaxseed is the richest source
of ALA in the North American diet-ALA constitutes 57% of the
total fatty acids in flaxseed.4, 5 It is also the
richest source of lignans, pro viding 75-800 times more lignans
than other plant foods such as legumes, cereals, vegetables and
fruits.6 ALA and lignans appear to influence inflammatory
responses by different mechanisms.
Atherogenesis and the
Inflammatory Response
The earliest changes in
atherogenesis occur in the arterial endothelium. For reasons
that are not entirely clear, the endothelium becomes more permeable
to lipoproteins and immune system cells such as monocytes, T
lymphocytes and leukocytes. The migration of these immune cells
into arterial walls is mediated by oxidized low-density lipoprotein
(LDL), cytokines and other blood factors. (Cytokines are proteins
synthesized and released by macrophages, leukocytes, neutrophils
and other cells; they both initiate and amplify inflammatory
responses.7)
Fatty streaks consisting
of lipid- and cholesterol-rich monocytes, macrophages and T lymphocytes
begin to form in arteries. This process is stimulated by the
adherence and aggregation of platelets and by several mediators
of the inflammatory response, including growth factors, cytokines
such as interleukin-1 and
tumor necrosis factor, and thrombaxane A2 an eicosanoid
derived from arachidonic acid. Refer to the table for a list of key
inflammatory mediators.
With continued inflammation,
the fatty streaks progress to advanced, complicated lipid-filled
lesions. Eventually, a fibrous cap forms. Formation of the
fibrous cap represents a healing response to the injury and
is mediated by the actions of interleukin-1, tumor necrosis
factor and other cytokines. When the advanced lesion becomes
unstable, the plaque ruptures, causing a thrombosis that may
result in myocardial infarction or stroke.2
Flaxseed Reduces Inflammatory
Responses
Flaxseed inhibits the production of pro-inflammatory
eicosanoids, such as thrombozane A2, and other lipid mediators, such as platetet-activating factor
(PAF). (PAF is a biologically active compound that is derived
from arachidonic acid and is involved in many immunopathological
reactions.) Flaxseed also inhibits the release of several inflammatory
cytokines-namely, tumor necrosis factor-o (TNF-a), interleukin-1ß (IL-1ß)
and interleukin-6 (IL-6).8, 9 Cytokines and lipid
mediators derived from arachidonic acid have been implicated
in the pathology and development of certain clinical features
of chronic inflammatory diseases such as systemic lupus erythematosus
(SLE)10 and rheumatoid arthritis.11 For
example, PAF production is increased and its catabolism decreased
in patients with SLE.8
Caughey and co-workers12 demonstrated
that consumption of flaxseed oil by healthy men for four weeks
reduced the production thrombozane B2, prostglandin
E2, TNF-alpha and IL-1beta by about 30%. (Thromboxane B2 is
an inactive metabolite of thromboxane A2.) The
flaxseed oil used in this study provided
about 14 g ALA per day, but it contained a negligible amount
of the lignans, which are nearly completely removed during
the oil-refining process. Caughey's findings agree with those
of other studies showing anti-inflammatory effects of omega-3
fatty acids in animals and humans.13
Clark and co-workers14 showed
that PAF-induced platelet aggregation was inhibited significantly
in nine patients who consumed 15 g or 30 g flaxseed daily for
four weeks. The patients all met the criteria for the diagnosis
of SLE. In rat models of renal diseases characterized by glomerular
scarring and poor renal function, whole flaxseed and flaxseed
oil retarded the progression of renal injury and the decline
in renal function.15, 16 A 15% flaxseed diet also
inhibited PAF-induced platelet aggregation in mice.16
Mechanisms of Action of Flaxseed's Constituents
The constituents in
flaxseed that exhibit anti-inflammatory actions are ALA and
lignans. ALA and the other omega-3 fatty acids block the conversion
of linoleic acid, an essential omega-6 fatty acid, to arachidonic
acid, and they inhibit the synthesis of pro-inflammatory eicosanoids
derived from arachidonic acid. ALA is itself converted to the
long-chain fatty acid eicosapentaenoic acid (EPA). EPA is converted
to eicosanoids that are less biologically active than those
derived from arachidonic acid and hence do not promote inflammation
and platelet aggregation.17
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Flaxseed lignans
are PAF-receptor antagonists and
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thus block
the pro-inflammatory actions of PAF.16
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Furthermore, lignans
may act like other antioxidants in
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blocking the oxidation
of LDL particles and decreasing
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their deposition
in arterial walls. The oxidation of LDL
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is believed to be
a key pathological event in the
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development of atherosclerosis.18
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Regular Flaxseed
Consumption May Have
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Long-term Benefits
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Flaxseed inhibits
the production of major systemic
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markers of inflammation,
including pro-inflammatory
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eicosanoids, cytokines
and platelet-activating factor.
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These effects have
been demonstrated in animals,
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healthy volunteers
and in patients diagnosed with
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systemic lupus erythematosus.
A regular intake of
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flaxseed may help
treat coronary heart disease and
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stroke by reducing
blood cholesterol levels, and it may
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help retard the
progression of atherosclerosis by
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reducing inflammatory
responses.
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References
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1.
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Berenson GS, et al. Am
J Cardiol. 1998;82:22T-29T.
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2.
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Ross R. New Engl J Med. 1999;340:115-126.
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3.
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Serraino M and Thompson LU. Cancer Lett. 1991;60:135-142.
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4.
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Daun JK and DeClercq DR. Proc Flax Institute. 1994;
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55:192-200.
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5.
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Connor WE. Am J Clin Nutr. 1999;69:827-828.
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6.
|
Thompson LU. In: Flaxseed
in Human Nutrition,
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Cunnane SC and Thompson
LU, eds. Champaign, IL:
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AOCS Press, 1995,
pp. 219-236.
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7.
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Laskin DL and Pendino KJ. Annu Rev Pharmacol Toxicol.
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1995;35:655-677.
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8.
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Tetta C, et al. Int Arch
Allergy Appl Immunol. 1990;91:
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244-256.
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9.
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O'Neill LAJ. Biochem Soc
Trans. 1997;25:295-301.
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10.
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Mohan IK and Das UN. Prostaglandins Leuko Essent Fatty
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Acids. 1997;56:193-198.
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11.
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Das
UN. Prostaglandins Leuko Essent
Fatty Acids.
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1991;44:201-210.
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12.
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Caughey GE, et al. Am J
Clin Nutr. 1996;63:116-122.
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13.
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Blok WL, et al. J Nutr. 1996;126:1515-1533.
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14.
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Clark WF, et al. Kidney
Int. 1995;48:475-480.
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15.
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Ingram AJ, et al. Am J
Kidney Dis. 1995;25:320-329.
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16.
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Hall AV, et al. Am J Kidney
Dis. 1993;22:326-332.
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17.
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Heller A, et al. Drugs. 1998;55:487-496
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18.
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Spencer AP, et al. Arch
Intern Med. 1999;159:1313-1320.
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19.
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Anisman H, et al. Can Med
Assoc J. 1996;155:1075-1082.
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20.
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Rotondo D. Biochem Soc
Trans. 1995;23:291-296.
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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/
