Flax Oil Capsules [Discontinued] by Genestra Brands

POSSIBLY INEFFECTIVE

• Hyperlipidemia. Clinical research suggests that alpha-linolenic acid does not lower lipid levels in adults with hyperlipidemia. Details: A meta-analysis of 20 small clinical trials in patients with hyperlipidemia shows that taking foods or supplements containing alpha-linolenic acid does not reduce lipid levels when compared with control (104256). The findings from this analysis are limited by the heterogeneity of the alpha-linolenic acid supplementation regimens and patient populations.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Atherosclerosis. Some research suggests that increasing dietary alpha-linolenic acid intake may decrease atherosclerosis. Details: Epidemiological research in White adults has found that high dietary intake of linolenic acid is associated with reduced calcified atherosclerotic plaques in the coronary arteries. Most dietary linolenic acid is alpha-linolenic acid (only a small fraction is gamma-linolenic acid). For every gram of linolenic acid consumed, risk of coronary artery calcification appears to decrease by 62% (12990). The effects of linolenic acid intake in other populations are unclear.
• Atopic dermatitis (eczema). Although there is interest in using oral alpha-linolenic acid (ALA) for atopic dermatitis, there is insufficient reliable information about the clinical effects of ALA for this condition.
• Attention deficit-hyperactivity disorder (ADHD). It is unclear if alpha-linolenic acid is beneficial in patients with ADHD. Details: Small clinical trials show that taking alpha-linolenic acid does not improve symptoms of previously untreated ADHD in children aged 6-16 years. Taking alpha-linolenic acid 1 gram daily for 8 weeks, or taking a combination of alpha-linolenic acid 60 mg, linoleic acid 240 mg, mineral oil 95 mg, and alpha-tocopherol 5 mg twice daily for 7 weeks does not affect ADHD symptom scores when compared with placebo (100660,100661). However, these studies might have been inadequately powered to detect a difference between groups.
• Cancer. It is unclear if increased dietary intake of alpha-linolenic acid affects mortality in patients with cancer. Details: A large meta-analysis of prospective, observational studies has found that high dietary intake of alpha-linolenic acid is associated with a 6% increased risk of mortality from cancer when compared with low dietary intake of alpha-linolenic acid (106661).
• Cardiovascular disease (CVD). Population research has found that increased dietary intake of alpha-linolenic acid may have some benefit for CVD, but results from clinical research are generally less positive. Details: A large meta-analysis of prospective, observational studies has found that high dietary intake of alpha-linolenic acid is associated with an 8% or 11% reduced risk of mortality from CVD or coronary heart disease (CHD), respectively, when compared with low dietary intake of alpha-linolenic acid. A dose-response analysis and meta-analysis show that a 1-gram increase in daily dietary intake is associated with a 5% reduction in CVD mortality (106661,107741). Other population research has found that consumption of 1-2 grams of dietary alpha-linolenic acid daily is associated with a reduced risk of a first myocardial infarction (MI) by as much as 59% in both males and females (7152,7156). The risk of fatal ischemic heart disease is reduced by 65% in females (7153). In patients who have had a previous MI, following a Mediterranean diet rich in alpha-linolenic acid (1.2-1.6 grams daily) and low in saturated fat and cholesterol for 27 months appears to reduce the risk for a second MI by 73% and the risk for death from any cause by 70% when compared to the standard postinfarction diet (7150). Overall, increasing dietary intake of alpha-linolenic acid by 1-1.2 grams daily appears to reduce the risk of fatal coronary heart disease by 20% in people with no history of heart disease and by 20% or more in people with existing heart disease (12978,91403). However, clinical research has not supported these findings. A meta-analysis of a small number of low to moderate quality clinical studies shows that higher intake of alpha-linolenic acid has little to no benefit for primary prevention of CVD, and does not reduce all-cause mortality, CVD mortality, or CHD events. Any reductions in CVD mortality, arrhythmias, or CHD events in individual trials are very small (103955). This may be due in part to the difficulty in separating the effects of alpha-linolenic acid from those of other dietary, lifestyle, or drug interventions (12917). Some research suggests alpha-linolenic acid has a greater effect on coronary heart disease when intake of fish oils is low (12989).
• Chronic obstructive pulmonary disease (COPD). Although there is interest in using oral alpha-linolenic acid (ALA) for COPD, there is insufficient reliable information about the clinical effects of ALA for this condition.
• Cognitive function. It is unclear if oral alpha-linolenic acid improves cognitive function in healthy adults.
• Crohn disease. Although there is interest in using oral alpha-linolenic acid (ALA) for Crohn disease, there is insufficient reliable information about the clinical effects of ALA for this condition.
• Crohn disease. Although there is interest in using oral alpha-linolenic acid (ALA) for Crohn disease, there is insufficient reliable information about the clinical effects of ALA for this condition.
• Depression. It is unclear if oral alpha-linolenic acid is beneficial in patients with depression. Details: Clinical research in patients aged 60-80 years who have had a myocardial infarction shows that consuming margarine containing alpha-linolenic acid 2 grams daily for 40 months does not reduce symptoms of depression when compared with placebo margarine (104978).
• Diabetes. It is unclear if oral alpha-linolenic acid is beneficial in patients with diabetes. Details: Epidemiological research involving overweight and obese individuals has found that eating at least 1.69 grams alpha-linolenic acid daily is associated with a 45% to 47% reduced risk of developing type 2 diabetes when compared with eating only 0.73 grams daily. However, higher intake of alpha-linolenic acid does not appear to be associated with a reduced risk of diabetes in people who are not overweight (101025). In patients with diabetes, epidemiological research shows that lower intake of alpha-linolenic acid is associated with an increased risk of diabetic nephropathy (101024). However, a meta-analysis of clinical research in adults with diabetes who are stable on oral antidiabetic medications shows that adding alpha-linolenic acid 1.5-7.4 grams daily, in the form of flaxseed oil, walnuts, or chia seeds, to a regular diet for 2-12 months does not improve glycemic control when compared with placebo (98002).
• Influenza. Although there is interest in using oral alpha-linolenic acid (ALA) for influenza, there is insufficient reliable information about the clinical effects of ALA for this condition.
• Hypertension. Some research suggests that increasing dietary alpha-linolenic acid may decrease the risk of hypertension. Details: Epidemiological research has found that high dietary intake of linolenic acid is associated with a reduced risk of hypertension in White adults. Most dietary linolenic acid is alpha-linolenic acid (only a small fraction is gamma-linolenic acid). Eating a diet high in linolenic acid seems to reduce the risk of hypertension by about 33% (12991). The effects of linolenic acid intake in other populations are unclear.
• Kidney transplant. Observational research suggests that alpha-linolenic acid is not beneficial after a kidney transplant, and may actually increase the risk of mortality. Details: Epidemiological research has found that dietary intake of alpha-linolenic acid is not associated with improved graft function in kidney transplant. However, kidney transplant recipients in the highest tertile of alpha-linolenic acid intake appear to have a 2.2-fold increased risk of death from any cause when compared with those in the lowest tertile of dietary intake (98003). It is not clear whether this difference is specifically due to alpha-linolenic acid intake or to total fat intake.
• Migraine headache. Although there is interest in using oral alpha-linolenic acid (ALA) for migraine headache, there is insufficient reliable information about the clinical effects of ALA for this condition.
• Multiple sclerosis. Although there is interest in using oral alpha-linolenic acid (ALA) for MS, there is insufficient reliable information about the clinical effects of ALA for this condition.
• Overall mortality. It is unclear if increased dietary intake of alpha-linolenic acid affects all-cause mortality. Details: A large meta-analysis of prospective, observational studies has found that high dietary intake of alpha-linolenic acid is associated with a 10% reduced risk of all-cause mortality when compared with low dietary intake of alpha-linolenic acid. A dose-response analysis shows that a 1-gram increase in daily dietary intake is associated with a 5% reduction in overall mortality (106661). However, a meta-analysis of 250,000 individuals did not find an association between dietary alpha-linolenic acid intake and all-cause mortality (107741). The validity of this finding is limited by the use of dietary surveys to assess intake and the heterogeneity of the included studies.
• Prostate cancer. There is contradictory evidence about the role of alpha-linolenic acid in prostate cancer. Details: Some epidemiologic research suggests that high dietary intake of alpha-linolenic acid is associated with an increased risk for prostate cancer (1337,2558,7823,7147,12978). Other research suggests high intake or serum levels of alpha-linolenic acid is not associated with increased levels of prostate specific antigen (PSA) or the overall risk of prostate cancer (12961,15736,91402). However, it might increase the risk of advanced prostate cancer (12961). The best evidence to date, which comes from a meta-analysis of five prospective population studies, suggests that increasing intake of alpha-linolenic acid by 0.5 grams daily is associated with a modest 1% reduction in the risk of prostate cancer. However, this analysis is dominated by a single study. A meta-analysis of results from nine prospective population studies suggests that a 0.1% increase in blood levels of alpha-linolenic acid is not associated with prostate cancer risk (90677). Reasons for the discrepancies are not entirely clear, but the source of alpha-linolenic acid appears to be important. Alpha-linolenic acid from dairy and meat sources has been positively associated with prostate cancer. Alpha-linolenic acid from plant sources, such as flaxseed, may not affect prostate cancer risk (12909).
• Pneumonia. It is unclear if dietary alpha-linolenic acid reduces the risk for pneumonia. Details: Epidemiological research has found that increasing dietary alpha-linolenic acid consumption is associated with a reduced risk of community-acquired pneumonia (13760).
• Psoriasis. Although there is interest in using oral alpha-linolenic acid (ALA) for psoriasis, there is insufficient reliable information about the clinical effects of ALA for this condition.
• Respiratory tract infections. It is unclear if oral alpha-linolenic acid is beneficial for reducing the incidence of respiratory tract infections in children. Details: Preliminary clinical research in children aged 3-4 years shows that taking alpha-linolenic acid 855 mg, in combination with linoleic acid 596 mg daily from November through February in 2 consecutive years, might reduce the number of recurrent respiratory infections when compared with placebo (10785).
• Rheumatoid arthritis (RA). It is unclear if oral alpha-linolenic acid is beneficial in patients with RA. Details: Preliminary clinical research shows that taking an alpha-linolenic acid-rich oil (flaxseed oil) for 3 months does not improve symptoms or laboratory parameters of RA when compared with baseline or with a linoleic acid-rich oil (safflower oil) (5898).
• Systemic lupus erythematosus (SLE). Although there is interest in using oral alpha-linolenic acid (ALA) for SLE, there is insufficient reliable information about the clinical effects of ALA for this condition.
• Ulcerative colitis. Although there is interest in using oral alpha-linolenic acid (ALA) for ulcerative colitis, there is insufficient reliable information about the clinical effects of ALA for this condition. More evidence is needed to rate alpha-linolenic acid for these uses.

(Read more about ALPHA-LINOLENIC ACID (ALA))

POSSIBLY EFFECTIVE

• Constipation. Oral flaxseed is a bulk forming laxative that helps to relieve constipation. Details: Flaxseed is a source of dietary fiber and has a bulk forming laxative effect (6803,12910). One clinical study in healthy young adults shows that consuming muffins containing 25 grams of milled flaxseed twice daily for 4 weeks increases weekly bowel movements by 30% when compared to a control group (6803). Other clinical research in diabetic patients with constipation shows that taking flaxseed 10 grams twice daily for 12 weeks improves stool form and reduces constipation by a moderate amount when compared with placebo (101950). Furthermore, a small clinical study in patients in China with functional constipation shows that consuming brown flaxseed flour 50 grams in divided doses with meals daily for 4 weeks seems to modestly improve frequency of bowel movements and pain and reduce failure to evacuate when compared with taking lactulose 15 mL every morning (105474). Flaxseed has also been evaluated in combination with other natural ingredients. A preliminary clinical trial in elderly patients with mild constipation shows that eating yogurt containing galacto-oligosaccharide syrup (Elixor, Borculo Whey Products) 6 grams, prunes 6 grams, and flaxseed 3 grams twice daily for 3 weeks increases stool frequency when compared with a control yogurt (21191). It is unclear if the effects were due to flaxseed, other constituents, or the combination.
• Diabetes. Oral ground flaxseed modestly reduces blood glucose in patients with diabetes and pre-diabetes. It is unclear if oral whole flaxseed reduces blood glucose. Details: Most evidence from meta-analyses and clinical research in adults with prediabetes and diabetes shows that taking ground flaxseed reduces fasting blood glucose and insulin levels (21194,21196,26479,101950,111061). A meta-analysis of 7 small to moderate clinical trials shows that taking flaxseed, usually ground, 13 to 40 grams daily for 8-12 weeks has a small beneficial effect on fasting blood glucose, insulin, insulin resistance, and glycated hemoglobin (HbA1c), compared with no intervention or another fiber source. A sub-analysis shows that the benefit of flaxseed on fasting glucose levels remains in patients with type 2 diabetes (111061). Other research disagrees. A meta-analysis of three small clinical trials in patients with type 2 diabetes shows that taking flaxseed does not improve fasting blood glucose, insulin resistance, or HbA1c (111062). Another meta-analysis of 24 clinical studies involving 1,879 patients with and without diabetes shows that whole and ground flaxseed seem to reduce blood glucose levels by an average of 6 mg/dL and insulin levels by an average of 1 mIU/mL and modestly reduce insulin resistance when compared with control treatments such as wheat germ or raw rice. Whole and ground flaxseed were not shown to significantly reduce HbA1c when compared with control, although there was a non-significant trend towards a reduction (96428). Significant heterogeneity in study size and study population limit the validity of these findings. The effects of flaxseed lignan extract in patients with type 2 diabetes is unclear. A small clinical study in Chinese adults with type 2 diabetes show that using a specific standardized flaxseed lignan extract (Flax Essence, Jarrow Formulas) 600 mg three times daily, providing 360 mg secoisolariciresinol diglucoside, slightly reduces HbA1c when compared with placebo (16768). However, a small meta-analysis including this study shows that taking flaxseed lignans does not reduce fasting blood glucose or HbA1c (111062).
• Hypercholesterolemia. Oral whole and ground flaxseed modestly reduce lipid levels. Details: Most research shows that taking various flaxseed preparations 30-50 grams daily reduces total cholesterol by 5% to 15% and low-density lipoprotein (LDL) cholesterol by 8% to 18%, but does not seem to affect high-density lipoprotein (HDL) cholesterol, when compared with control (6808,10952,22179,26478,65866,101944,101947,101949,108044,108046)(111064). Apolipoprotein A-1 and apolipoprotein B may be reduced by 6% and 7.5%, respectively (10952). A meta-analysis of clinical studies shows reductions in apolipoprotein A and apolipoprotein B following whole flaxseed supplementation (108046). The cholesterol-lowering effect of flaxseed has been shown in various populations, including those with hypercholesterolemia with/or without diabetes, postmenopausal patients, and patients with chronic kidney disease or cardiovascular risk factors (6808,10952,10978,12910,22180,22181,26478,26480,26488,101944)(101949,101950,111064). One large meta-analysis suggests that the most consistent effect occurs in patients with hypercholesterolemia (101947). Another large meta-analysis suggests that patients with hypercholesterolemia and healthy patients with a body mass index greater than 25 kg/m2 may benefit the most from treatment (108044). Most research shows that flaxseed reduces triglyceride levels (101947,108046,111064). However, there are certain preparations, such as partially defatted flaxseed (which lacks alpha-linolenic acid content) or flaxseed incorporated into bread products, which might increase triglyceride levels by up to 26% (6808,26488).
• Hypertension. Daily oral flaxseed consumption, especially for longer than 12 weeks, seems to modestly reduce blood pressure. Details: Meta-analyses of mainly small clinical studies in patients with and without hypertension show that taking flaxseed reduces systolic and diastolic blood pressure by an average of 1.1 to 1.8 and 1.0 to 1.3 mmHg, respectively, when compared with control (96426,111063). The effect of flaxseed lignan is unclear. One meta-analysis shows that flaxseed lignan does not seem to reduce blood pressure when compared with control (96426). However, a more recent meta-analysis shows that taking flaxseed lignan has a small effect on systolic, but not diastolic, blood pressure (111063). The length of supplementation may play a role as studies lasting longer than 12 weeks seemed to lower blood pressure to a slightly greater degree than studies lasting less than 12 weeks (96426). The validity of these findings is limited due to the short duration of treatment, the variation in study size, the inclusion of patients with and without hypertension, and the range of doses used. Some clinical research also shows that taking flaxseed may be beneficial for blood pressure reduction in patients with hypertension (111063). One individual clinical study in adults with hypertension shows that taking flaxseed 10 grams or 30 grams daily affects blood pressure in a dose-dependent manner when compared with placebo. After 12 weeks of treatment, systolic and diastolic blood pressure decreased by 12 mmHg and 6 mmHg, respectively, in the high-dose group, compared with 10 mmHg and 7 mmHg, respectively, in the low-dose group (108043).
• Mastalgia. Oral flaxseed seems to reduce symptoms of cyclic mastalgia. Details: Clinical research in healthy Iranian women with cyclic mastalgia shows that taking flaxseed powder 25 grams daily for 2 months reduces breast pain intensity from moderate to mild and also reduces duration of pain when compared with placebo (96250). Other preliminary clinical research shows that eating a muffin containing ground flaxseed 25 grams daily for 3 months reduces symptoms of severe cyclic mastalgia (16766).
• Obesity. Oral flaxseed and flaxseed mucilage seem to modestly improve weight loss in patients who are obese or overweight. However, flaxseed lignan extract does not seem to be beneficial. Details: A meta-analysis of 45 clinical studies including 2,561 overweight or obese adults shows that flaxseed consumption reduces body weight by 1.8 kg, body mass index (BMI) by 0.6 kg/m2, and waist circumference by 1.2 cm when compared with control in adults. The most benefit is seen in adults with a baseline BMI greater than or equal to 27 (96427). Flaxseed consumption of at least 30 grams daily for durations of at least 12 weeks demonstrated the greatest efficacy (96427,101949). The soluble fiber, flaxseed mucilage, has also been studied. A clinical trial in overweight or obese adults shows that taking oral flaxseed mucilage 1280 or 2560 mg mixed in water twice daily with meals for 12 weeks decreases body weight, waist circumference, and BMI in a dose-dependent manner when compared with placebo. After 12 weeks, a 5 kg and 4 kg weight reduction was observed in the high- and low-dose groups, respectively, compared to a 1 kg reduction in the placebo group (108047). The validity of this finding is limited due to short duration of treatment and lack of follow-up. Conversely, flaxseed lignan extract does not appear to be effective in reducing weight, BMI, or waist circumference (96427). Some research has investigated whether variants in genes related to satiety and appetite play a role in any effect of flaxseed on weight loss and appetite. A small clinical trial in adults with overweight or obesity shows that taking defatted flaxseed flour in biscuits daily for 8 weeks modestly reduces body weight, BMI, triglycerides, or blood glucose only in those with specific gene variants when compared with control biscuits (111066). More information is needed to determine how these gene variants play a role in the connection between nutrition and obesity.
• Systemic lupus erythematosus (SLE) nephritis. Oral flaxseed might be beneficial for improving kidney function in SLE. Details: Some small clinical studies suggest that taking whole or ground flaxseed orally might improve serum creatinine levels in people with SLE nephritis (6802,8021).

POSSIBLY INEFFECTIVE

• Osteoporosis. Oral flaxseed does not seem to be beneficial in osteoporosis. Details: Clinical research shows that consuming ground flaxseed 40 grams daily for up to one year does not affect markers of bone metabolism or improve bone mineral density in healthy, postmenopausal adults (10952,12910). Similarly, taking flaxseed extract 550 mg three times daily for 6 months does not appear to improve bone mineral density when compared with placebo in older adults (21197).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Although there is interest in using oral flaxseed for acne, there is insufficient reliable information about the clinical effects of flaxseed for this purpose.
• Benign prostatic hyperplasia (BPH). It is unclear if oral flaxseed lignan improves symptoms of BPH. Details: A small clinical study in patients with BPH shows that taking a specific flaxseed lignan extract (BeneFlax, Archer Daniels Midland Co.) 300 mg or 600 mg daily for 4 months improves lower urinary tract symptom scores when compared with placebo. Additionally, the 600 mg dose was associated with improved quality of life when compared with placebo (21193).
• Breast cancer. It is unclear if oral flaxseed reduces the risk for breast cancer or the progression of breast cancer. Details: A small clinical study in females newly diagnosed with breast cancer shows that consuming a muffin containing ground flaxseed 25 grams daily for about 40 days reduces markers of tumor cell proliferation when compared with baseline, but not when compared with placebo (16765). The effect of flaxseed intake on breast cancer outcomes was not assessed. Dietary lignans, which occur in flaxseed, have been linked with a lower risk of developing breast cancer. Most large-scale population studies have found that high intake of dietary lignans and serum levels of the lignan enterolactone are associated with a reduced risk of developing breast cancer (16775,16776,16777,16779,16781,16782,16783,16785). It is unclear if flaxseed lignan, specifically, is beneficial for reducing the risk of breast cancer.
• Burning mouth syndrome. Flaxseed has only been evaluated in a mouthwash in combination with German chamomile; its effect when used alone is unclear. Details: A small clinical study in female patients with burning mouth syndrome shows that using a homemade mouthwash containing boiled whole flaxseed 10 grams and German chamomile 1 gram in 200 mL of water 3-4 times daily for 3 months decreases subjective burning and dry mouth symptoms, increases salivary flow rate, and decreases saliva viscosity when compared with baseline (104807). However, the validity of these results is limited by the lack of a control group and product standardization, as the mouthwash was prepared by each patient from ingredients they purchased.
• Cardiovascular disease (CVD). It is unclear if oral flaxseed or flaxseed lignans reduce the development or progression of CVD. Details: A small clinical study in older adults that were also given dietary advice shows that taking flaxseed 30 grams daily for 12 weeks, starting 4 weeks after percutaneous coronary intervention (PCI), more than doubles flow mediated dilation when compared with a group not taking flaxseed (101945). However, population research has found that total dietary intake of lignans, including flaxseed lignans, is not associated with a reduced risk of coronary heart disease or all-cause mortality (16787). This research did not specifically assess the effect of flaxseed intake on CVD.
• Chronic kidney disease (CKD). Although there is interest in using oral flaxseed for CKD, there is insufficient reliable information about the clinical effects of flaxseed for this condition.
• Colorectal cancer. It is unclear if oral flaxseed reduces the risk of colorectal cancer. Details: Flaxseed is one source of dietary lignans. Population research has found that serum levels of lignans are not associated with risk of developing colorectal cancer (16778). However, other population research has found that high dietary intake of lignans is associated with a reduced risk of colorectal cancer (16784), and that higher serum levels of dietary lignans are associated with a reduced risk of colorectal adenomas (16788). It is unclear if flaxseed lignan, specifically, is beneficial for reducing the risk of colorectal cancer.
• Endometrial cancer. It is unclear if oral flaxseed reduces the risk of endometrial cancer. Details: Flaxseed is one source of dietary lignans. A large-scale population study has found that serum levels of lignans are not associated with risk of developing endometrial cancer (16786).This research did not specifically assess the effect of flaxseed intake on endometrial cancer risk.
• Fatigue. It is unclear if oral ground flaxseed reduces fatigue in overweight children. Details: A small non-blinded clinical study in overweight healthy children ages 7-18 shows that consuming ground flaxseed 20 grams in divided doses with food daily for 4 weeks seems to modestly reduce mental fatigue but not physical fatigue when compared with puffed wheat 25 grams daily (105473).
• Impaired glucose tolerance (prediabetes). It is unclear if oral flaxseed is beneficial in prediabetes. Details: A small clinical study in adults with prediabetes shows that consuming milled flaxseed 20 grams or 40 grams daily for 12 weeks does not improve glycemic control, but modestly reduces systolic blood pressure, when compared with no intervention (96434).
• Irritable bowel syndrome (IBS). It is unclear if oral flaxseed improves IBS symptoms. Details: A small open-label clinical study in patients with IBS suggests that consuming whole or ground flaxseed 24 grams daily for 4 weeks does not improve quality of life, severity of IBS symptoms, or number of bowel movements when compared with no intervention (21198).
• Lung cancer. It is unclear if oral flaxseed reduces the risk of lung cancer. Details: Observational research has found that consuming a higher amount of dietary phytoestrogens, such as the lignan metabolites and precursors found in flaxseed, is associated with a lower risk of developing lung cancer when compared to those who consume smaller amounts (13190). It is unclear if flaxseed, specifically, is beneficial for reducing the risk of lung cancer.
• Menopausal symptoms. There is contradictory evidence about the effects of flaxseed for reducing menopausal symptoms. Details: Some preliminary clinical research in postmenopausal adults shows that taking either flaxseed meal 90 grams daily or a specific flaxseed extract (Biogalenica, Medicinal Compounding Pharmacy) 1000 mg daily for 6 months reduces menopausal symptoms and the frequency of hot flashes when compared to baseline (21200). Other small clinical studies in postmenopausal adults show that consuming ground flaxseed orally 40 grams daily reduces symptoms of hot flashes by about 35% and night sweats by about 44% when compared to baseline (10978,12910). However, similar reductions have been observed with placebos, such as wheat germ (12910,18224). Higher quality studies of flaxseed used in food products have yielded negative results. One clinical trial in postmenopausal adults shows that taking a specific flaxseed-containing bar (Glambia Nutritionals) providing 7 grams of flaxseed and 410 mg of lignans reduces hot flash frequency by 28% and hot flash scores by 50% when compared to baseline, but not when compared with placebo (18224). In another small clinical study, consuming muffins containing flaxseed 25 grams daily providing 50 mg lignans did not improve hot flashes or measures of quality of life when compared with placebo in a similar patient population (16762). Eating flaxseed-enriched bread providing 25 grams of flaxseed daily for 12 weeks also did not improve menopausal symptoms or reduce the frequency of hot flashes when compared to control (22176).
• Metabolic syndrome. Small studies suggest that oral flaxseed is beneficial for metabolic syndrome. Details: One small clinical study in older adults shows that taking a specific flaxseed lignan extract (BeneFlax, Archer Daniels Midland Co.) 550 mg three times daily for 6 months reduces metabolic syndrome risk scores when compared with placebo in males, but not females (21197). Another small open-label clinical trial in patients with metabolic syndrome suggests that taking flaxseed powder 30 grams daily for 12 weeks modestly reduces the number of people meeting the criteria for metabolic syndrome when compared with no supplementation (105276). However, food containing flaxseed does not seem to be as beneficial. Some clinical research in Asian Americans with metabolic syndrome shows that eating bread containing flaxseed 30 grams daily plus lifestyle counseling for 12 weeks does not improve markers of metabolic syndrome when compared with lifestyle counseling alone (21199).
• Nonalcoholic fatty liver disease (NAFLD). Small clinical studies suggest that oral flaxseed may modestly reduce markers of liver disease progression in patients with NAFLD. Details: A small clinical pilot study in adults with NAFLD shows that taking brown milled flaxseed 30 grams daily for 12 weeks along with lifestyle modification reduces fibrosis by 21% and steatosis by about 15.3%, compared with reductions of 9.7% and 5.5%, respectively, in those following lifestyle modifications alone (96249). A larger follow-up clinical study in patients with NAFLD shows that taking brown milled flaxseed 30 grams daily for 12 weeks in addition to lifestyle modification reduces steatosis by about 28%, compared with a 16% reduction in the lifestyle modification group (105275).
• Osteoarthritis. It is unclear if topical flaxseed is beneficial in patients with osteoarthritis. Details: A small clinical study in patients with hand osteoarthritis who are using routine treatments shows that using a flaxseed poultice compress once daily for 7 days improves pain by 63% and hand function by 66% when compared with a hot compress or no compress in combination with routine treatments. Some of the benefit was maintained for at least a week following treatment (101946).
• Peripheral arterial disease (PAD). It is unclear if oral flaxseed is beneficial in patients with PAD. Details: Clinical research in patients with PAD shows that taking milled flaxseed 30 grams daily mixed with a variety of foods for one year does not reduce the incidence of cardiac arrhythmias or improve the distance walked until claudication when compared with placebo (101942). This study may have been inadequately powered to detect differences between groups.
• Pharyngitis. Although there is interest in using oral flaxseed for pharyngitis, there is insufficient reliable information about the clinical effects of flaxseed for this purpose.
• Polycystic ovary syndrome (PCOS). It is unclear if oral flaxseed is beneficial in patients with PCOS. Details: A small open-label clinical study in patients with PCOS shows that taking flaxseed 30 grams daily for 12 weeks in conjunction with receiving lifestyle modification advice reduces triglyceride and insulin levels and improves insulin resistance when compared with lifestyle modification advice alone. About 69% of those in the treatment group who had irregular menstrual cycles at baseline had a regular cycle at the end of treatment, compared with no significant improvement in the control group. Flaxseed did not affect body weight, low-density lipoprotein (LDL) cholesterol, or blood glucose when compared with control (101943).
• Prostate cancer. Small clinical studies suggest that oral flaxseed may modestly improve biomarkers of prostate cancer. Details: A very small clinical trial in patients with prostatic intraepithelial neoplasia (PIN), a precancerous proliferation of prostatic epithelial cells, shows that adding ground flaxseed (Alena, Enreco) 30 grams daily to a fat-restricted diet for 6 months lowers prostate specific antigen (PSA) levels and slows prostate epithelium proliferation when compared with baseline (12908). This finding is limited by the lack of a placebo group. A clinical study in patients with prostate cancer awaiting prostatectomy shows that taking ground flaxseed (Alena, Enreco) 30 grams daily with or without a fat-restricted diet for about 30 days reduces tissue proliferation rate, but does not reduce PSA, when compared with control (16761).
• Radiation-induced pneumonitis. It is unclear if oral flaxseed is beneficial for preventing radiation-induced pneumonitis in patients with non-small cell lung cancer (NSCLC). Details: A very small, clinical trial in adults with locally advanced or metastatic NSCLC currently undergoing chemoradiation therapy shows that taking ground flaxseed (Golden Valley Flax; Hylden Farms) 40 grams daily, starting one week prior to radiotherapy and continuing until completion of treatment, may reduce the risk of radiation-induced pneumonitis when compared with baseline, with only 1 patient (5%) developing a grade ≥3 event and no cases of grade 2 events (108042). The validity of these findings is limited by the lack of a comparator group and a low adherence rate due to tolerability issues.
• Rheumatoid arthritis (RA). It is unclear if oral flaxseed is beneficial in patents with RA. Details: A clinical study in adults with RA shows that following either a regular or anti-inflammatory diet supplemented with oral flaxseed 30 grams daily for 12 weeks improves disease activity score 28-joint (DAS28-ESR), as well as pain and quality of life outcomes, such as emotional well-being and vitality, when compared with baseline (108048). The validity of these findings is limited by the lack of a comparator group.
• Ulcerative colitis. It is unclear if oral flaxseed is beneficial in patients with ulcerative colitis. Details: A small open-label clinical study in patients with ulcerative colitis shows that taking ground flaxseed 30 grams daily for 12 weeks seems to modestly reduce inflammatory markers and disease severity and improve quality of life when compared with control (101941). A nonblinded, clinical study in adults with mild to moderate ulcerative colitis shows that taking brown milled flaxseed 15 grams twice daily for 12 weeks improves disease severity scores when compared with placebo (108045). The validity of these findings is limited by the lack of blinding and short duration of treatment. More evidence is needed to rate flaxseed for these uses.

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POSSIBLY EFFECTIVE

• Coronary heart disease (CHD). Supporting, but not conclusive, evidence suggests that consuming fats and oils rich in oleic acid might reduce the risk of CHD (26466,95745,98563,101821). However, the relationship between blood levels of oleic acid and risk of CHD or CVD is unclear (101832,101834,101838). In 2018, the US Food and Drug Administration (FDA) determined that it would allow a qualified health claim stating that replacing dietary fats and oils higher in saturated fat with oils containing at least 70% oleic acid may reduce the risk of CHD. To achieve this benefit, high-oleic acid containing oils should not increase total daily energy intake. The suggested daily dietary intake is about 20 grams (1.5 tablespoons) of high oleic acid oils in place of other fats and oils. These oils include olive oil, high-oleic acid sunflower oil, and high-oleic acid canola oil (98563). A meta-analysis of clinical studies shows that replacing 7.5% of energy from partially hydrogenated vegetable oils with high oleic acid sunflower oil can reduce coronary heart disease risk by about 9% to 19%. Furthermore, analysis of results from observational studies found that replacing partially hydrogenated oil with high oleic acid sunflower oil is associated with a 16% to 35% reduction in the risk of coronary heart disease events (95745). Clinical research in patients with cardiovascular disease (CVD) risk shows that taking high-oleic acid canola oil 60 grams per 3000 kcal of energy daily as part of a fixed composition diet for 4-6 weeks reduces the Framingham 10-year coronary heart disease risk scores by 6.8% compared to baseline (26466,101821). However, taking the high-oleic acid canola oil is no more effective than regular canola oil, which contains approximately 62% oleic acid (26466,101821). The relationship between blood levels of oleic acid and risk of CHD or CVD is unclear. While some population research has found that having the highest blood levels of oleic acid is associated with an increased risk of CVD when compared to having the lowest blood levels of oleic acid, other research suggests an inverse association or no association at all (101832,101834,101838). One study has found that having the highest blood levels of oleic acid is associated with a 1.4- to 2-fold increased risk of heart failure, other cardiovascular events, and all-cause mortality (101832). In contrast, another found that the highest blood levels of oleic acid is associated with a 73% reduced risk of having a stroke (101838). A third study found no association at all between plasma levels of oleic acid and risk of heart failure (101834). The clinical significance of these findings is unclear, and results should not necessarily be extrapolated to dietary oleic acid (101832). While plasma oleic acid levels seem to be a weak indirect marker of moderate to high olive oil use, it is also a weak marker of intake of butter and avian fats (101838). Furthermore, there is no clear evidence that plasma levels of oleic acid directly correlate with dietary oleic acid, especially where dietary oleic acid intake is relatively low (101832). As a non-essential fatty acid, oleic acid is endogenously synthesized in the liver from saturated fats (101832,101834,101838).
• Hypercholesterolemia. Evidence from small studies shows that consuming oils rich in oleic acid as part of the diet in place of other dietary fats may improve cholesterol levels (21698,26466,67569,101821). Preliminary clinical research in patients with hypercholesterolemia shows that consuming oleic acid as part of a high oleic sunflower oil- or high oleic canola oil-rich diet for 3-4 weeks decreases total and low-density lipoprotein (LDL) cholesterol levels by a moderate amount when compared with diets rich in palm oil, medium-chain triglycerides, or a blend of fats found in a regular Western diet (21698,67569). Other clinical research in patients with at least one cardiovascular risk factor shows that consuming oleic acid as part of high oleic acid canola oil for up to 4 weeks reduces total cholesterol by up to 9.4% and LDL cholesterol by up to 12.5% compared to baseline or a diet higher in saturated fats. However, taking the high oleic acid canola oil is no more effective than regular canola oil, also a source of oleic acid (26466,101821).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Bladder cancer. Population research has found that the highest blood levels of oleic acid are associated with a 46% decreased risk of having bladder cancer when compared to the lowest blood levels (101844). However, plasma oleic acid levels are only a weak indirect marker of dietary intake of oleic acid. As a non-essential fatty acid, oleic acid is endogenously synthesized in the liver from saturated fats (101832,101834,101838). The effect of oleic acid supplementation on bladder cancer risk is unknown.
• Breast cancer. Population research has found no association between dietary fatty acid intake, including oleic acid, and the risk of breast cancer (96528). The effect of oleic acid supplementation on breast cancer risk is unknown.
• Depression. An observational study in perimenopausal patients aged 42-52 years has found that increasing dietary intake of oleic acid is associated with an increase in depression symptom scores. The odds ratio for depressive symptoms was approximately 2-fold higher for the highest quartile of oleic acid intake when compared with the lowest quartile (108924).
• Diabetes. A small clinical trial in patients with type 2 diabetes shows that taking oleic acid as part of a low-fat diet containing 15% monounsaturated fatty acids for 3 weeks does not alter levels of total or low-density lipoprotein (LDL) cholesterol or the change in LDL oxidation when compared with taking linoleic acid as part of a low-fat diet containing 15% polyunsaturated fatty acids (101847).
• Diarrhea. Preliminary clinical research in patients with chronic diarrhea shows that taking oleic acid 1.6 or 3.2 mL before a meal reduces bowel movements over the next 24 hours by approximately 22% compared with taking no oleic acid. Intestinal transit time was also increased by 28 and 54 minutes, respectively (101848). Since the specific cause of chronic diarrhea differed among the patients included in this study, it is unclear if oleic acid is beneficial for most or only certain forms of chronic diarrhea.
• Hypertension. Preliminary clinical research in patients with central obesity and at least one other cardiovascular disease risk factor shows that taking oleic acid as high oleic acid canola oil for 4 weeks does not reduce systolic or diastolic blood pressure compared to baseline (26466).
• Obesity. Preliminary clinical research in patients with central obesity shows that taking oleic acid as high oleic acid canola oil for 4 weeks reduces abdominal fat mass by approximately 0.1 kg compared to baseline (98564). Other preliminary clinical research in patients with central adiposity and at least one other risk factor of cardiovascular disease shows that taking high oleic acid canola oil for 6 weeks reduces total and low-density lipoprotein (LDL) cholesterol by 3.4% and 5.6%, respectively, compared with a control oil lower in monounsaturated fats and higher in saturated fats (101821). However, in these studies, taking the high oleic acid canola oil is no more effective than regular canola oil, also a source of oleic acid (98564,101821). Any effect of oleic acid itself is unclear.
• Pancreatic cancer. The association between dietary oleic acid and pancreatic cancer risk is unclear. Most population research shows no association between dietary oleic acid and pancreatic cancer risk. However, one large population study has found that the highest intake of oleic acid, at least 23.7 grams daily, is associated with a 71% decreased risk of pancreatic cancer when compared with the lowest intake. The benefit is only observed in overweight or obese individuals. (101833). The effect of oleic acid supplementation on pancreatic cancer risk is unknown.
• Short bowel syndrome. A small preliminary clinical trial in patients with surgical short bowel syndrome of at least 2 years shows that taking oleic acid 3.2 mL in 50 mL of a beverage daily for 3 months does not reduce intestinal transit time or diarrhea, or improve body weight, when compared with placebo. In addition, energy absorption was reduced by 14% (101843).
• Stroke. Population research has found that highest blood levels of oleic acid are associated with a 73% reduced risk of stroke when compared with lowest blood levels of oleic acid (101838). However, plasma oleic acid levels are only a weak indirect marker of dietary oleic acid. As a non-essential fatty acid, oleic acid is endogenously synthesized in the liver from saturated fats (101832,101834,101838). The effect of oleic acid supplementation on stroke risk is unknown.
• Ulcerative colitis. Although some contradictory evidence exists, a large population study has found that, after adjusting for dietary intake of omega-3 fatty acids, highest dietary intake of oleic acid is associated with a 97% reduced odds of developing ulcerative colitis when compared with the lowest intake (101846). The effect of oleic acid supplementation on ulcerative colitis risk is unknown.

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LIKELY SAFE ...when used orally in amounts typically found in foods (7141,7142,7144). There is insufficient reliable information available about the safety of alpha-linolenic acid when used in larger, medicinal amounts.

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts typically found in foods (7141,7142,7145). There is insufficient reliable information available about the safety of alpha-linolenic acid during pregnancy and lactation when used in larger, medicinal amounts; avoid using.

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LIKELY SAFE ...when ground flaxseed is used orally and appropriately. Ground flaxseed has been safely used in numerous clinical trials in doses up to 30-60 grams daily for up to 1 year (6803,6808,8020,10952,10978,12908,12910) (16760,16761,16762,16765,16766,18224,21191,21194,21196,21198) (21199,21200,22176,22179,22180,22181,65866,66065) (101943,101949,101950).

POSSIBLY SAFE ...when flaxseed lignan extract or mucilage is used orally and appropriately. Some clinical research shows that a specific flaxseed lignan extract (Flax Essence, Jarrow Formulas) 600 mg daily can be used with apparent safety for up to 12 weeks (16768). Additional clinical research shows that other flaxseed lignin extracts can be used with apparent safety for up to 6 months (21193,21197,21200). In one clinical trial, flaxseed mucilage was used with apparent safety at a dose of up to 5120 mg daily for up to 12 weeks (108047)....when flaxseed is used topically in a warm poultice (101946).

POSSIBLY UNSAFE ...when raw or unripe flaxseed is used orally. Raw flaxseed contains potentially toxic cyanogenic glycosides (linustatin, neolinustatin, and linamarin); however, these glycosides have not been detected after flaxseed is baked (5899). Unripe flaxseeds are also thought to be poisonous when consumed due to cyanide content.

PREGNANCY: POSSIBLY UNSAFE
when used orally. Flaxseed can have mild estrogenic effects. Theoretically, this might adversely affect pregnancy (9592,12907); however, there is no reliable clinical evidence about the effects of flaxseed on pregnancy outcomes.

LACTATION:
Insufficient reliable information available; avoid using.

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LIKELY SAFE ...when used orally in food amounts. Edible oils containing high amounts of oleic acid are commonly used in foods (26466,90681,94452,101821,101824,101828,101830,101838). There is insufficient reliable information available about the safety of oleic acid when used as medicine.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using in amounts greater than those commonly found in foods.

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ANTIBIOTIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, antibiotics might interfere with the metabolism of flaxseed constituents, which could potentially alter the effects of flaxseed.  Details Some potential benefits of flaxseed are thought to be due to its lignan content. Secoisolariciresinol diglucoside (SDG), a major lignan precursor, is found in high concentrations in flaxseed. SDG is converted by bacteria in the colon to the lignans enterolactone and enterodiol (5897,8022,8023,9592). Antibiotics alter the flora of the colon, which could theoretically alter the metabolism of flaxseed.

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Theoretically, using flaxseed in combination with anticoagulant or antiplatelet drugs might have additive effects and increase the risk of bleeding.  Details Some clinical evidence suggests that the oil contained in flaxseed can decrease platelet aggregation (5898,21912).

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Theoretically, flaxseed might have additive effects when used with antidiabetes drugs and increase the risk for hypoglycemia.  Details Some clinical research suggests that flaxseed can lower blood glucose levels (5899,10978,21194,21196,111061).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, flaxseed might have additive effects when used with antihypertensive drugs and increase the risk of hypotension.  Details Clinical research shows that daily flaxseed consumption, especially for longer than 12 weeks, modestly reduces blood pressure (21197,26487,96426,96428,111063).

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking flaxseed might decrease the effects of estrogens.  Details Flaxseed contains lignans with mild estrogenic and possible antiestrogenic effects. The lignans seem to compete with circulating endogenous estrogen and might reduce estrogen binding to estrogen receptors, resulting in an anti-estrogen effect (8868,9593). It is unclear if this effect transfers to exogenously administered estrogens.

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General ...Orally, alpha-linolenic acid from dietary sources is well tolerated when used in the diet as a replacement for other sources of fat, such as saturated fats.
Serious Adverse Effects (Rare):
Orally: There is some concern that high dietary intake of alpha-linolenic acid might increase the risk for prostate cancer, although research is conflicting.

Oncologic ...Epidemiologic research suggests that high dietary intake of alpha-linolenic acid might increase risk for prostate cancer (1337,2558,7823,7147,12978). Other research suggests high intake or serum levels of alpha-linolenic acid does not increase the overall risk of prostate cancer (12961,15736); however, it might increase the risk of advanced prostate cancer (12961). Association with prostate cancer appears to depend on the sources of alpha-linolenic acid. Dairy and meat sources has been positively associated with prostate cancer, whereas plant sources, such as flaxseed, don't seem to affect prostate cancer risk (12909). According to a clinical trial, intake of alpha-linolenic acid does not appear to increase levels of prostate specific antigen (PSA) (91402). Also, longer-chain omega-3 fatty acids in fish oils are associated with a decreased risk of total and advanced prostate cancer (12961).

Other ...Alpha-linolenic acid is a type of fat, containing 9 kilocalories/gram, and may result in weight gain if consumed in excess. Patients should be advised that it's best to substitute alpha-linolenic acid in the diet for other sources of fat, such as saturated fats.

(Read more about ALPHA-LINOLENIC ACID (ALA))

General ...Orally, flaxseed is usually well-tolerated.
Most Common Adverse Effects:
Orally: Bloating, diarrhea, gastrointestinal complaints.
Serious Adverse Effects (Rare):
Orally: Severe allergic reactions such as and anaphylaxis.

Gastrointestinal ...Integrating flaxseed in the diet can cause digestive symptoms similar to other sources of dietary fiber including bloating, fullness, flatulence, abdominal pain, diarrhea, constipation, dyspepsia, and nausea (12910,16761,16765,21198,21200,22176,22179,65866,101943). Higher doses are likely to cause more gastrointestinal side effects. Flaxseed can significantly increase the number of bowel movements and the risk for diarrhea (6803,8021,16765). Doses greater than 45 grams per day may not be tolerated for this reason (6802). Metallic aftertaste and bowel habit deterioration have also been reported in a clinical trial (21198).
There is some concern that taking large amounts of flaxseed could result in bowel obstruction due to the bulk forming laxative effects of flaxseed. Bowel obstruction occurred in one patient in a clinical trial (65866). However, this is not likely to occur if flaxseed is consumed with an adequate amount of fluids.

Immunologic ...Occasionally, allergic and anaphylactic reactions have been reported after ingestion of flaxseed (16761). Handling and processing flaxseed products might increase the risk of developing a positive antigen test to flaxseed and hypersensitivity (6809,12911,26471,26482).

Oncologic ...Flaxseed contains alpha-linolenic acid (ALA). High dietary intake of ALA has been associated with increased risk for prostate cancer (1337,2558,7823,7147,12978). However, ALA from plant sources, such as flaxseed, does not seem to increase this risk (12909).

Other ...Orally, partially defatted flaxseed, which is flaxseed with less alpha-linolenic acid, might increase triglyceride levels (6808). Raw or unripe flaxseed contains potentially toxic cyanogenic glycosides (linustatin, neolinustatin, and linamarin). These chemicals can increase blood levels and urinary excretion of thiocyanate in humans. However, these glycosides have not been detected after flaxseed is baked (5899).

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General ...Orally, oleic acid generally well tolerated when used as part of oils and fats in the diet (26466,90681,94452,101821,101824,101828,101830,101838). Temporary burning in the mouth or throat has occurred in some patients (101848).

Gastrointestinal ...Orally, oleic acid has caused temporary burning in the mouth or throat in some patients in one clinical study (101848).

(Read more about OLEIC ACID)