Scientific Name(s): Linum usitatissimum L. Family: Linaceae
Common Name(s): Flax , flaxseed , linseed , lint bells , linum 1
Flaxseed and flaxseed oil contain various essential fatty acids but are particularly rich in alpha linolenic acid (ALA), an omega-3 fatty acid and precursor to the longer and less saturated omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Flaxseed (but not flaxseed oil) also contains high fiber that may have health benefits similar to other high-fiber products and phytoestrogens that may exert weak estrogenic or antiestrogenic effects depending on biological levels of estradiol. Historically, linseed oil, derived from flaxseed, has been used as a topical demulcent and emollient, as a laxative, and as a treatment for coughs, colds, and urinary tract infections. More recently, flaxseed has been investigated for protection against atherosclerotic cardiovascular disease, including reduction of serum cholesterol, platelet aggregation, and inflammatory markers; chemoprotection against some cancers; improvement of menopausal symptoms; improvement of attention deficit hyperactivity disorder (ADHD) symptoms; and renoprotection in patients with systemic lupus erythematosus (SLE). However, clinical trials are limited.
Flaxseed has been given in clinical trials at doses from 15 to 50 g/day. Flaxseed oil supplementation equivalent to 200 mg of ALA content has been given.
Contraindicated in patients with known hypersensitivity to flaxseed.
The use of flaxseed and flaxseed oil during pregnancy and lactation is not recommended.
None well documented.
Flaxseed and flaxseed oil appear to be well tolerated, with few adverse reactions reported except type 1 hypersensitivity.
Ingestion of large amounts of raw flax or flaxseed may be harmful because of cyanogenic glycosides. These glycosides have not been detected after flaxseed has been baked.
The flax plant is a slender annual that grows to 0.3 to 0.9 m in height. It branches at the top and has small, pale-green alternating leaves. Flax was introduced to North America from Europe and now grows widely in Canada and the northwestern United States. Each branch is tipped with 1 or 2 delicate blue flowers that bloom from February through September. 2 Additional members of the genus Linum are used throughout the world for their fiber and oil content.
Flax has been used for nearly 12,000 years as a source of fiber for producing linen 2 , 3 and was one of the earliest plants used for purposes other than food. Flax is processed from the fibers in the stem of the plant. 4 Flaxseed or linseed oil, derived from flaxseed, has been used as a topical demulcent and emollient and as a laxative, particularly for animals. Flaxseed oil also is used in paints and varnishes and as a waterproofing agent. Flaxseed cakes have been used as cattle feed.
Traditional medicinal uses of the plant have been varied and, at times, unusual; one text notes use of the seed for removing foreign material from the eye. A moistened seed was placed under the closed eyelid for a few moments to allow the material to adhere to the seed, thereby facilitating removal. 5 Other uses include the treatment of coughs and colds, constipation, and urinary tract infections. 2 The related Linum catharticum yields a purgative decoction. 5
The medical properties of flax are primarily associated with the seed. Flaxseed is composed of multiple chemical constituents, the mechanisms of which are slowly being analyzed. 6 Studies have attributed different medicinal properties to unsaturated fatty acids (mainly ALA and linoleic acid), lignans (predominantly secoisolarciresinol diglucoside), and nonstarch polysaccharides (ie, gum, fiber). 3 Flax produces a seed that contains 38% to 45% oil. Also known as linseed oil, it is obtained by crushing and compressing the seeds. The oil is composed of approximately 70% polyunsaturated fatty acids, including linolenic, linoleic, and oleic acids 7 ; approximately 18% monounsaturated fatty acids; and approximately 9% saturated fatty acids. Flaxseed or linseed oils are among the best natural sources of ALA, an omega-3 fatty acid. 8 Linoleic acid, a rich source of omega-6 fatty acid, and ALA are critical for the structural integrity of cell membranes. ALA is a precursor to the longer and more unsaturated omega-3 fatty acids EPA and DHA; however, only a modest amount of ALA appears to be converted to these longer chain fatty acids. 9
Whole or ground flaxseed is a rich source of lignans, including secoisolariciresinol and matairesinol. These lignans are believed to exert antioxidant and phytoestrogenic effects. They are converted by bacteria in the colon to the active metabolites enterodiol and enterolactone. 7 , 10 , 11 These metabolites are reported to have greater antioxidant activity than the parent lignan secoisolarciresinol diglucoside 12 and also exert either a weak estrogenic or an antiestrogenic effect, depending on the biological levels of estradiol. 3 , 13
Whole or ground flaxseed is a source of a soluble fiber mucilage that is also found in other members of the Linum genus. This gum-like material contains polysaccharides containing D-xylose, L-rhamnose, L-galactose, arabinose, D-galacturonic and mannuronic acids, fucose, and glucuronic acid. 3 , 14 , 15 Flaxseed may also contain phenylpropanoids (eg, p -coumaric, o -coumaric, linusitamarin). 7 , 16 The nutrient composition of the 3 forms of flaxseed differ. Flaxseed oil differs from whole and ground flaxseed because it is devoid of fiber and lignans. 8 Flax leaves and seed chaff contain the cyanogenic glycosides linamarin, linustatin, and neolinustatin, which can increase blood levels and urinary excretion of the thiocyanate in humans consuming raw flax or flaxseed and cause toxicity in grazing animals as cyanide is released from these compounds when the tissues are crushed. 5 , 17 These glycosides have not been detected after flaxseed has been baked. 17
Uses and Pharmacology
The German Commission E sanctioned the use of flaxseed for the treatment of chronic constipation, colons damaged by laxative abuse, irritable colon, and diverticulitis. It also is approved as a mucilage for gastritis and enteritis. When used externally, it is approved as a poultice for local inflammation. 18 However, with a clearer understanding of the various groups of constituents that may contribute to the therapeutic effects of flaxseed, many additional studies have been performed in the last decade.
ALA has been studied in numerous clinical trials, and health benefits are most likely related to a more favorable omega-6 to omega-3 fatty acid intake (ie, increased omega-3 intake). 3 Whether this is relevant to the mechanism by which flaxseed exerts any of its beneficial effects is unclear. 8
The active metabolites, enterodiol and enterolactone, are reported to have greater antioxidant activity than their parent lignan, secoisolarciresinol diglucoside. 12 They also exert estrogenic or antiestrogenic properties, depending on the biological levels of estradiol. 13 At normal estradiol levels, the lignans act as estrogen antagonists, but in postmenopausal women with low estradiol levels, they can act as weak estrogens. 8 Other activities related to estrogen include the in vivo synthesis of 2-hydroxy estrogen, a compound that may protect against cancer 19 and inhibit the binding of estrogen and testosterone to receptors on sex-binding globulin. 20 Flaxseed may also exert health benefits similar to those of other high-fiber products: lowering the risk of colon cancer, lowering cholesterol, and improving glycemic tolerance. 3 , 21Cardiovascular effects
Flaxseed may protect against atherosclerotic cardiovascular disease (ASCVD) through a number of mechanisms, including reducing serum cholesterol, platelet aggregation, and inflammatory markers; improving glucose tolerance; and acting as an antioxidant. 8 Daily consumption of 15 to 50 g/day of ground flaxseed can modestly reduce total cholesterol and low-density lipoprotein (LDL) concentrations without altering triglycerides or high-density lipoprotein cholesterol (HDL-C); however, the exact mechanism is unclear. 8 While preliminary data on the effectiveness of flaxseed products in improving ASCVD risk appear promising, randomized, controlled clinical trials are needed to establish efficacy on a wider range of surrogate markers. 8Effects on serum cholesterol
Interest has centered on the ability of diets rich in flax to improve the blood lipid profile. The fiber content is thought to be important for flaxseed's lipid-lowering effect, 22 with evidence also suggesting that secoisolarciresinol diglucoside may directly lower serum cholesterol. 23 Lignans may be able to decrease serum cholesterol by modulating the enzymes and acyl CoA cholesterol transferase, both of which are involved in cholesterol metabolism. 8 The ALA content appears to be less likely to lower cholesterol. Partially defatted flaxseed may also lower cholesterol, 24 while flaxseed oil (containing no fiber or lignans) did not alter any lipid parameters in a 12-week study in healthy volunteers. 25Animal data
One study in hypercholesterolemic rabbits showed that using a lignan complex isolated from flaxseed resulted in a reduction in oxidative stress and serum total cholesterol, LDL cholesterol and total cholesterol/HDL-C ratio, and increased serum HDL-C. 26Clinical data
When 15 hypercholesterolemic subjects consumed 3 slices of bread containing flaxseed plus 15 g of ground flaxseed daily for 3 months, serum total and LDL cholesterol levels were significantly reduced ( P < 0.01); however, HDL cholesterol levels did not change. These changes suggest improvement in plasma lipid profile. 22
A double-blind, crossover study was conducted comparing the effects of whole flaxseed and sunflower seed on serum LDL cholesterol levels in 38 postmenopausal women. Patients were randomized to consume 38 g of flaxseed or sunflower seed baked into muffins and bread daily for 6 weeks. The treatment consisted of a 6-week trial, followed by a 2-week washout period and then another 6 weeks of treatment. Blood samples were collected at baseline and during weeks 6, 8, and 14. The flaxseed regimen significantly ( P < 0.001) lowered LDL cholesterol (14.7%) compared with baseline, but no statistically significant difference was obtained when compared with the sunflower seed regimen. 27
In another study, when healthy women supplemented their diet with 50 g of ground flaxseed daily for 4 weeks, ALA levels in plasma and erythrocytes increased; serum total cholesterol decreased 9% and LDL cholesterol was reduced 18%. 17
More recent studies continue to support the suggestion that whole flaxseed or its powder (15 to 50 g/day) can modestly reduce total cholesterol and LDL in both hypercholesterolemic 14 , 15 , 20 , 25 , 28 and normocholesterolemic 11 , 29 , 30 individuals without affecting HDL or triglycerides. 8 However, 2 recent studies reported opposite effects.
One study found only a short-lived LDL cholesterol-lowering effect in 62 hyperlipidemic men and postmenopausal women treated with 40 g/day of ground flaxseed-containing products while following a low-fat, low-cholesterol diet. 31 Conversely, another study showed that American Indian postmenopausal women benefitted from 30 g/day of flaxseed in their diet. Total cholesterol and LDL cholesterol were lowered by approximately 7% and 10%, respectively, while HDL and triglycerides remained unchanged. 32
An 8-week, randomized, double-blind, placebo-controlled trial was conducted in 55 hypercholesterolemic subjects using placebo and 300 and 600 mg/day dietary secoisolarciresinol diglucoside extracted from flaxseed. At 6 and 8 weeks, the 600 mg/day of secoisolarciresinol diglucoside resulted in a decrease in total cholesterol (22%) and LDL cholesterol (24%). 33Antioxidant effects
Omega-3 fatty acids have been shown to suppress oxygen-free radicals from neutrophils and monocytes, as well as the production of interleukin-1, tumor necrosis factor, and leukotriene B4. 34
Secoisolarciresinol diglucoside is metabolized in the body to the lignans enterodiol and enterolactone. The in vitro antioxidant activity of enterodiol and enterolactone is 3 times greater than that of secoisolarciresinol diglucoside and inhibits peroxidation of polyunsaturated fatty acids, 12 which may decrease oxidation of LDL, a key player in atherogenesis. 8Animal data
Results from an in vitro study in Zucker rats suggest that secoisolarciresinol diglucoside may reduce oxidative stress in type 2 diabetes. 36 Another study demonstrated that cardiac cellular damage was attenuated when dogs were given an endotoxin with flaxseed versus endotoxin alone. 37Clinical data
Human intervention trials have not revealed any antioxidant effects to date. In 62 hyperlipidemic men and postmenopausal women treated for 10 weeks with 40 g/day of ground flaxseed-containing products, the markers for oxidative stress (ie, LDL, urinary isoprostanes) were not affected at any point during the study. 31 In a 12-week study in healthy volunteers, flaxseed oil (containing no fiber or lignans) produced no change in oxidative modification of LDL cholesterol. 26Platelet aggregation and inflammatory markers
Flaxseed contains ALA and linoleic acid that, once ingested, can be converted to different fatty acids that yield different classes of the eicosanoids, which have different effects on inflammation, platelet aggregation, and vasoconstriction. ALA is converted to EPA and DHA, which produce eicosanoids involved in decreased platelet aggregation, vasoconstriction, and thrombosis. Linoleic acid is converted to arachidonic acid, which produces eicosanoids with opposite effects. 8 The ALA pathway is likely to be predominant in producing beneficial cardiovascular effects. Flaxseed contains high levels of the lignan precursor secoisolarciresinol diglucoside, which is associated with anti-inflammatory activity 38 and has been shown to act as an antagonist of platelet-activating factor. 39Clinical data
While theoretical mechanisms of action and epidemiological data point to a potential platelet inhibitory effect of ALA, 40 human studies have not shown a consistent antiplatelet effect. 8 When 15 hypercholesterolemic subjects consumed 3 slices of bread containing flaxseed plus 15 g of ground flaxseed daily for 3 months, thrombin-stimulated platelet aggregation decreased with the flax supplement. 22 Another study reported that 40 g of flaxseed oil over 23 days produced an increase in the platelet EPA to arachidonic acid ratio, which suggests that flaxseed oil may decrease the tendency of platelets to aggregate. 41
However, other studies using flaxseed oil have not found an antiplatelet effect, 26 , 42 and human studies have not shown an effect on anti-inflammatory markers. In 62 hyperlipidemic men and postmenopausal women treated for 10 weeks with 40 g/day of ground flaxseed-containing products, the inflammatory markers (IL-6, Hs-CRP) were not affected at any point during the study. 31 In another study, low doses of ALA (3.5 g/day) from flaxseed oil given for 12 weeks did not affect cytokine production, mononuclear cell subsets, or lymphocyte proliferation. 43 In a study of 179 healthy menopausal women, flaxseed and placebo treatments did not change C-reactive protein levels after 12 months of therapy. 44 However, 1 study demonstrated that ALA supplementation lowered the serum concentrations of inflammatory markers more profoundly when background diet was rich in saturated fatty acids and lacking in monounsaturated fatty acids (ie, Western diets). 45Cancer prevention
Phytoestrogens and ALA have been purported to have cancer protective effects 19 , 20 , 46 , 47 ; however, the mechanism by which these compounds exert their chemoprotective effect has not been completely explained. 3 , 48 It may be related to antioxidant properties, to an effect on hormone metabolism, or to the anti-angiogenic effects of lignans, or to any combination of these. 3
Various studies support the chemoprotective effect of flaxseed and also various mechanisms of action.Breast cancer
In a small study in newly diagnosed postmenopausal breast cancer patients, dietary flaxseed showed positive effects on tumor biological markers compared with placebo, including a reduction in Ki-67 labeling index (a measure of the rate of tumor cell proliferation), a reduction in c-erbB2 score, and an increase in apoptosis index. 49
In a randomized, crossover trial in 28 postmenopausal women, consumption of flaxseed 5 or 10 g/day in addition to usual diets decreased serum 17-beta-estradiol and estrone sulfate concentrations and increased serum prolactin concentrations. 20 Enterolactone and enterodiol may decrease cell proliferation and inhibit aromatase, 5-alpha-reductase, and 17-beta-hydroxysteroid dehydrogenase activity, which may offer a reduction in the risk of breast, prostate, and other hormone-sensitive cancers. 20 In a meta-analysis of epidemiological studies of the composition of fatty acids in biological samples, 3 cohort studies showed a protective effect for omega-3 fatty acids but an increase in breast cancer risk for monounsaturated fatty acids in pre- and postmenopausal women. 50 Total saturated fatty acids were associated with breast cancer risk only in postmenopausal women. 50 In 7 case-control studies, the only finding was for ALA, which showed an inverse association bordering on statistical significance. 50Prostate cancer
Data are conflicting. In a recent study in men with prostate cancer awaiting surgery, flaxseed 30 g/day for 30 days slowed tumor growth by 40% to 50% compared with those on a low-fat diet and placebo. 51 This supports the results of 2 previous studies showing beneficial effects of flaxseed combined with a low-fat diet on prostate cancer. In 1 small study, prostate cancer cell proliferation decreased and apoptosis increased in men ingesting flaxseed 30 g/day. 52 A subsequent study found flaxseed in combination with a low-fat diet to control prostate growth. Prostate-specific antigen level and cell proliferation decreased from baseline after only 6 months on the dietary regimen. 53
These findings are in contrast to previous epidemiologic evidence suggesting that ALA increases the risk for prostate cancer 51 , 54 ; however, flaxseed was not the source of ALA in these studies. 51 The antioxidant properties and the antiangiogenic effects of lignans cannot be excluded as the mechanism by which flaxseed may exert its beneficial effect on prostate cancer. 51Lung cancer
Epidemiological evidence suggests that people who consume a higher amount of dietary phytoestrogens, such as lignan metabolites and precursors found in flaxseed, might have a lower risk of developing lung cancer compared with those who consume smaller amounts. 55Other cancers
Soluble fiber and other components of flaxseed fractions could potentially affect insulin secretion and its mechanisms of action in maintaining plasma glucose homeostasis and may, therefore, decrease postprandial glucose response 25 and improve glucose tolerance. 8 Many studies in animal models support this hypothesis 3 ; however, clinical data are lacking.Clinical data
A reduction in blood glucose and insulin levels was observed in a randomized crossover study of 25 postmenopausal women fed a flaxseed 40 g/day fortification diet or hormone replacement therapy. 57 In 62 hyperlipidemic men and postmenopausal women, one study found that consumption of 40 g/day of ground flaxseed-containing products reduced the homeostatic model assessment of insulin resistance. 31
An 8-week, randomized, double-blind, placebo-controlled trial was conducted in 55 hypercholesterolemic subjects using placebo and 300 and 600 mg/day dietary secoisolarciresinol diglucoside extracted from flaxseed. At 6 and 8 weeks, the 600 mg/day of secoisolarciresinol diglucoside resulted in approximately 25% lowering of fasting plasma glucose concentrations, especially in those subjects with baseline glucose concentrations greater than or equal to 5.83 mmol/L. 33 In contrast to ground flaxseed and secoisolarciresinol diglucoside, ALA did not regulate glucose levels in elderly people fed 3 g/day 58 and type 2 diabetes patients fed 35 mg/kg body weight, 59 suggesting that the fatty acid component of flaxseed has no effect on insulin and glucose.Menopausal symptoms
The photoestrogenic effects of flaxseed may benefit women suffering from menopausal symptoms. However, data is limited on the efficacy of flaxseed on the consequences of estrogen deficiency in menopausal women. 60Clinical data
Administration of flaxseed 40 g/day appears to be as effective as oral hormone replacement therapy for improving mild menopausal symptoms. 57 In another study, flaxseed 40 g/day reduced severity scores for hot flushes by 35% and night sweats by 44%, but the wheat germ placebo produced similar improvements in symptoms. 60 Similarly, a study comparing dietary wheat (placebo), soy (25 g/day), and flaxseed muffins (25 g/day) resulted in less severe hot flushes with flaxseed but no other changes in symptoms. 61
A study of 30 women suffering at least 14 hot flushes per week for at least 1 month who took flaxseed 40 g/day resulted in a mean decrease in hot flush scores after flaxseed of 57% (median decrease, 62%). The mean reduction in daily hot flush frequency was 50% (median reduction, 50%), from 7.3 to 3.6 hot flashes. 62Other uses
Attention deficit hyperactivity disorder
ADHD is commonly associated with decreased blood omega-3 fatty acid levels. 63 A pilot study evaluated the effect of ALA-rich supplementation with flax oil and antioxidant emulsion on blood fatty acid composition and behavior in children with ADHD. Postsupplementation levels of red blood cell membrane fatty acids were higher than pretreatment and control levels. There was an improvement in the symptoms of ADHD reflected by reduction in total hyperactivity scores of ADHD children. 64Lupus nephritis
Glomerulonephritis is a common and serious complication of SLE, and flaxseed has shown potential to help patients who develop lupus nephritis. 65 Preliminary evidence derived from a mouse model of lupus indicates that diets supplemented with 15% flaxseed for 14 weeks delayed the onset of proteinuria and reduced overall mortality compared with controls. 39 Flaxseed contains high levels of the lignan precursor secoisolarciresinol diglucoside, which is associated with anti-inflammatory activity (eg, formation of less inflammatory classes of renal prostanoids), 38 thus offering a renoprotective effect. 66 Nine patients with SLE taking part in a single-blind, randomized clinical trial who received flaxseed 30 g/day and prednisone for 1 year, followed by crossover to a year without flaxseed supplementation, experienced improvements in renal function. 30
Flaxseed (whole or ground) has been given in doses of 25 to 40 g/day in clinical trials and showed benefit in postmenopausal women suffering hot flushes. 57 , 60 , 61 , 62 Flaxseed (whole or ground) has been used in 1 clinical trial showing renoprotective effects in SLE patients at doses of 30 g/day. 30
Flax oil supplementation equivalent to 200 mg of ALA content (combined with vitamin C 25 mg ) was given twice daily in a clinical trial of ADHD children. 64
The US Food and Drug Administration has not granted a GRAS (Generally Recognized as Safe) status to flaxseed or flaxseed oil, although it does allow up to 12% flaxseed in food by weight. 6 However, based on available data, it appears that flaxseed and its oil are safe in doses of up to 50 g/day.
The use of flaxseed or its oil during pregnancy and lactation is not recommended. 6 , 67 Animal studies show possible harmful effects, and there are insufficient human data. 6 , 68 Flaxseed may stimulate menstruation or exert other hormonal effects and could be detrimental in pregnancy. 6
Flaxseed, but not flaxseed oil, contains mucilage; thus, absorption of coadministered drugs may be impaired. 6 Oral drugs should be taken 1 hour before or 2 hours after flaxseed to prevent decreased absorption. 6
Theoretically, flaxseed and flaxseed oil may potentiate the effects of anticoagulants, antiplatelet agents, nonsteroidal anti-inflammatory drugs, antihyperlipidemic agents, antihypertensive agents, and mood stabilizer agents; however, no clinical cases have been reported. 6
Flaxseed, but not flaxseed oil, by virtue of its fiber content may increase or enhance the effects of laxatives. 29 Because of its phytoestrogen content, it may exhibit weak estrogenic or antiestrogenic effects and therefore has the potential to interact with oral contraceptives or hormone replacement therapy. 6
Type 1 hypersensitivity to flaxseed (linseed) oil has been confirmed; therefore, it is contraindicated in patients with known hypersensitivity. 6 In a case report, a 40-year-old man experienced acute dyspnea without bronchospasm 2 to 3 minutes after eating multigrain bread; type 1 hypersensitivity to linseed was later confirmed. 69 There has also been a report of ocular pruritus and weeping following ingestion of linseed oil; type 1 hypersensitivity to linseed was later confirmed. 70 Handling and processing flax products might increase the risk of developing a positive antigen test to flaxseed and hypersensitivity. 70 Approximately 50% of workers exposed to flax demonstrated immunologically positive antigen tests in one survey. 71
In the few case reports and clinical trials available in humans, flaxseed and flaxseed oil appear to be well tolerated, with few adverse reactions reported. 6 Many of the adverse reactions reported have been associated with allergy to flaxseed. 6 These include palmar pruritus, generalized urticaria, nausea/vomiting, intestinal/abdominal pain, diarrhea, hydrorrhea, successive sneezing, nasal obstruction, and intense general malaise. 6 , 69 , 70
Flaxseed, but not flaxseed oil, can cause digestive symptoms similar to other dietary fibers, including bloating, flatulence, abdominal pain, diarrhea, dyspepsia, and nausea. 60 Anecdotally, intestinal obstruction may occur from mass effect when large amounts of flaxseed, but not flaxseed oil, are ingested or taken with an inadequate amount of water. 6 In theory, consumption of flaxseed or flaxseed oil may prevent episodes of mania or hypomania in bipolar patients. 72
The cyanogenic properties of some flax constituents theoretically suggest that ingestion of large amounts of the plant may be harmful; however, this is primarily a veterinary problem encountered in grazing animals. These glycosides have not been detected after flaxseed has been baked. 17
Anecdotally, an overdose of flaxseed or its oil may result in weakness, unstable gait, paralysis, or seizures. 69 The physiologic balance between ALA and linoleic acid may be relevant, and ALA deficiency may cause neurologic abnormalities. 73
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