Effects of a Flaxseed-Derived Lignan Supplement in Type 2 Diabetic Patients: A Randomized, Double-Blind, Cross-Over Trial High dose flaxseed oil supplementation may affect fasting blood serum glucose management in human type 2 diabetics. Dietary Milled Flaxseed and Flaxseed Oil Improve N-3 Fatty Acid Status and Do Not Affect Glycemic Control in Individuals with Well-Controlled Type 2 Diabetes The effect of flaxseed powder on insulin resistance indices and blood pressure in prediabetic individuals: A randomized controlled clinical trial Daily flaxseed consumption improves glycemic control in obese men and women with pre-diabetes: a randomized study. Effects of Soy-Soluble Fiber and Flaxseed Gum on the Glycemic and Insulinemic Responses to Glucose Solutions and Dairy Products in Healthy Adult Males Dietary modulation of the gut microbiota – a randomised controlled trial in obese postmenopausal women High alpha-linolenic acid flaxseed (Linum usitatissimum): some nutritional properties in humans. Flaxseed influences urinary lignan excretion in a dose-dependent manner in postmenopausal women. Flaxseed supplementation improved insulin resistance in obese glucose intolerant people: a randomized crossover design Flaxseed on cardiovascular disease markers in healthy menopausal women: a randomized, double-blind, placebo-controlled trial. Effects of flaxseed consumption on systemic inflammation and serum lipid profile in hemodialysis patients with lipid abnormalities Effect of flaxseed oil on serum systemic and vascular inflammation markers and oxidative stress in hemodialysis patients: a randomized controlled trial Flaxseed and Cardiovascular Risk Factors: Results from a Double Blind, Randomized, Controlled Clinical Trial Effects of brown and golden flaxseed on the lipid profile, glycemia, inflammatory biomarkers, blood pressure and body composition in overweight adolescents. Impact of weight loss diet associated with flaxseed on inflammatory markers in men with cardiovascular risk factors: a clinical study The relative bioavailability of enterolignans in humans is enhanced by milling and crushing of flaxseed. Flaxseed Supplementation (Not Dietary Fat Restriction) Reduces Prostate Cancer Proliferation Rates in Men Presurgery No evidence of hypoglycemia or hypotension in older adults during 6 months of flax lignan supplementation in a randomized controlled trial: A safety evaluation Dietary walnuts inhibit colorectal cancer growth in mice by suppressing angiogenesis. Evaluation of the efficacy of flaxseed meal and flaxseed extract in reducing menopausal symptoms. Health aspects of partially defatted flaxseed, including effects on serum lipids, oxidative measures, and ex vivo androgen and progestin activity: a controlled crossover trial. Effects of n-3 fatty acid supplements on glycemic traits in Chinese type 2 diabetic patients: A double-blind randomized controlled trial. Dietary flaxseed independently lowers circulating cholesterol and lowers it beyond the effects of cholesterol-lowering medications alone in patients with peripheral artery disease. Dietary flaxseed lignan extract lowers plasma cholesterol and glucose concentrations in hypercholesterolaemic subjects. Systemic inflammation and carotid diameter in obese patients: pilot comparative study with flaxseed powder and cassava powder. Effects of hempseed and flaxseed oils on the profile of serum lipids, serum total and lipoprotein lipid concentrations and haemostatic factors
Background Flaxseed consumption has been shown to improve blood lipids in humans and flaxseed-derived lignan has been shown to enhance glycemic control in animals . The study aim ed to investigate the effect of a flaxseed-derived lignan supplement on glycemic control , lipid profiles and insulin sensitivity in type 2 diabetic patients . Methodology /Principal Findings This was a r and omized , double-blind , placebo-controlled , cross-over trial and it was conducted between April and December 2006 in Shanghai , China . Seventy-three type 2 diabetic patients with mild hypercholesterolemia were enrolled into the study . Patients were r and omized to supplementation with flaxseed-derived lignan capsules ( 360 mg lignan per day ) or placebo for 12 weeks , separated by an 8-week wash-out period . HbA1c , lipid profiles , insulin resistance index and inflammatory factors were measured . Sixty-eight completed the study and were included in the analyses . The lignan supplement significantly improved glycemic control as measured by HbA1c ( -0.10±0.65 % vs. 0.09±0.52 % , P = 0.001 ) compared to placebo ; however , no significant changes were observed in fasting glucose and insulin concentrations , insulin resistance and blood lipid profiles . Urinary excretion of lignan metabolites ( enterodiol and enterolactone ) was significantly higher after the lignan supplement intervention compared to baseline ( 14.2±18.1 vs. 1.2±2.4 µg/mL , P<0.001 ) . Data also suggested minimal competition between lignan and isoflavones for bioavailability when measured by the excretion concentrations . Conclusions / Significance Daily lignan supplementation result ed in modest , yet statistically significant improvements in glycemic control in type 2 diabetic patients without apparently affecting fasting glucose , lipid profiles and insulin sensitivity . Further studies are needed to vali date these findings and explore the efficacy of lignans on type 2 diabetes . Trial Registration Clinical Trials.gov Type 2 diabetes is characterized partially by elevated fasting blood serum glucose and insulin concentrations and the percentage of hemoglobin as HbA1c . It was hypothesized that each of blood glucose and its co-factors insulin and HbA1c and would show a more favorable profile as the result of flaxseed oil supplementation .  Patients were recruited at r and om from a population pool responding to a recruitment advertisement in the local newspaper and 2 area physicians . Completing the trial were 10 flaxseed oil males , 8 flaxseed oil females , 8 safflower ( placebo ) oil males and 6 safflower oil females . Patients visited on two pre-treatment occasions each three months apart ( visits 1 and 2 ) . At visit 2 subjects were r and omly assigned in double blind fashion and in equal gender numbers to take flaxseed oil or safflower oil for three further months until visit 3 . Oil consumption in both groups was approximately 10 g/d . ALA intake in the intervention group was approximately 5.5 g/d . Power was 0.80 to see a difference of 1 mmol of glucose /L using 12 subjects per group with a p < 0.05 . Flaxseed oil had no impact on fasting blood serum glucose , insulin or HbA1c levels . It is concluded that high doses of flaxseed oil have no effect on glycemic control in type 2 diabetics Objective : To determine the effects of dietary consumption of milled flaxseed or flaxseed oil on glycemic control , n-3 fatty acid status , anthropometrics , and adipokines in individuals with type 2 diabetes . Design : Thirty-four participants were r and omized into a parallel , controlled trial . Subjects : The participants were adults with type 2 diabetes ( age 52.4 ± 1.5 years , body mass index 32.4 ± 1.0 kg/m2 , n = 17 men and 17 women ) . Interventions : Participants consumed a selection of bakery products containing no flax ( control group [ CTL ] , n = 9 ) , milled flaxseed ( FXS , n = 13 ; 32 g/d ) , or flaxseed oil ( FXO , n = 12 ; 13 g/d ) daily for 12 weeks . The FXS and FXO groups received equivalent amounts of alpha-linolenic acid ( ALA ; 7.4 g/day ) . Measures of Outcome : The primary outcome measures were fasting plasma hemoglobin A1c , glucose , insulin , and phospholipid fatty acid composition . The secondary outcome measures were fasting circulating leptin and adiponectin , as well as body weight , body mass index , and waist circumference . Dietary intake assessment and calculations for homeostasis model assessment for insulin resistance and quantified insulin sensitivity check were also completed . Results : The FXS and FXO groups had increases in plasma phospholipid n-3 fatty acids ( ALA , eicosapentaenoic acid [ EPA ] , or decosapentaenoic acid [ DPA ] , but not docosahexaenoic acid ) , and the FXO group had more EPA and DPA in plasma phospholipids compared to the FXS group . All groups had similar caloric intakes ; however , the CTL group experienced a 4 % weight gain compared to baseline ( p < 0.05 ) , while both flax groups had constant body weights during the study period . All other parameters , including glycemic control , were unchanged by dietary treatment . Conclusions : Milled FXS and FXO intake does not affect glycemic control in adults with well-controlled type 2 diabetes . Possible prevention of weight gain by flax consumption warrants further investigation Background : Design ing the effective and early interventions can prevent progression of prediabetes to diabetes . Few studies have shown the effect of flaxseed on glycemic control . This study aim ed to assess the effect of flaxseed powder on insulin resistance ( IR ) indices and blood pressure in prediabetic individuals . Material s and Methods : In a r and omized clinical trial , 99 prediabetic individuals were r and omly divided into three groups : two groups received 40 g ( FG40 ) and 20 g ( FG20 ) flaxseed powder daily for 12 weeks and the third group was the control ( CG ) . Before and after the intervention , anthropometric measurements , blood pressure , fasting serum glucose ( FSG ) , insulin , homeostasis model assessment IR index ( HOMA-IR ) , beta-cell function , and insulin sensitivity were measured . Results : FSG significantly declined overall in all groups compared to the baseline ( P = 0.002 in CG and FG20 groups and P = 0.001 in FG40 ) . In contrast , mean of the changes in FSG was not significantly different between groups . Insulin concentration did not change significantly within and between the investigated groups . Although HOMA-IR reduced in FG20 ( P = 0.033 ) , the mean of changes was not significant between the three groups . Mean of beta-cell function increased in CG and FG40 groups compared to the baseline ( P = 0.044 and P = 0.018 , respectively ) , but mean of its changes did not show any difference between the three groups . The mean of changes in IR indices was not significant between the three groups . FG40 group had significantly lowered systolic blood pressure after the intervention ( P = 0.005 ) . Conclusion : Daily intake of flaxseed powder lowered blood pressure in prediabetes but did not improve glycemic and IR indices The study hypothesis was that fasting glucose , insulin , fructosamine , C-reactive protein , and interleukin-6 decrease and adiponectin increases with daily flaxseed consumption in overweight or obese individuals with pre-diabetes . In this r and omized , cross-over study overweight or obese men and postmenopausal women ( n = 25 ) with pre-diabetes consumed 0 , 13 , or 26 g ground flaxseed for 12 weeks . Glucose , insulin , homeostatic model assessment ( HOMA-IR ) , and normalized percent of α-linolenic fatty acid ( ALA ) were significantly different by treatment ( multiple analysis of variance , P = .036 , P = .013 , P = .008 , P = .024 respectively ) . Paired t tests showed glucose decreased on the 13 g intervention compared to the 0 g period [ 13 g = -2.10 ± 1.66 mg/L ( mean ± SEM ) , 0 g = 9.22 ± 4.44 mg/L , P = .036 ] . Insulin decreased on the 13 g intervention but not the 26 g ( P = .021 ) and 0 g ( P = .013 ) periods ( 13 g = -2.12 ± 1.00 mU/L , 26 g = 0.67 ± 0.84 mU/L , 0 g = 1.20 ± 1.16 mU/L ) . HOMA-IR decreased on the 13 g period but not on the 26 g ( P = .012 ) and 0 g ( P = .008 ) periods ( 13 g = -0.71 ± 0.31 , 26 g = 0.27 ± 0.24 , 0 g = 0.51 ± 0.35 ) . The α-linolenic fatty acid decrease for the 0 g period was different than the 13 g ( P = .024 ) and 26 g ( P = .000 ) periods ( 13 g = 0.20 ± 0.04 , 26 g = 0.35 ± 0.07 , 0 g = -0.01 ± 0.07 ) . Fructosamine , high sensitivity C-reactive protein , adiponectin , and high-sensitivity interleukin-6 had no significant  differences . Flaxseed intake  decreased glucose and insulin and improved insulin sensitivity as part of a habitual diet in overweight or obese individuals with pre-diabetes Objective : Soy-soluble polysaccharides and flaxseed gum are underutilized dietary fibers of interest to the food industry . However , because the ability of soluble fibers to modulate postpr and ial glucose and insulin metabolism has been related to their viscous effects , the utility of these and other low-viscosity soluble fibers remains unproven . The objective of this study was to examine the associations between soy-soluble polysaccharides and flaxseed gum concentration , product viscosity , and the postpr and ial glycemic and insulinemic responses in the context of glucose solutions as well as fluid and gelled dairy products . Methods : Twelve healthy males participated in a r and omized crossover postpr and ial study in which they visited the laboratory following overnight fasts on 11 occasions to consume one of 11 study treatments , each consisting of 50 g available carbohydrates . The study treatments included a glucose reference ( in duplicate ) , glucose solutions containing soy-soluble polysaccharides ( 6 % ) , flaxseed gum ( 0.7 % ) , or guar gum ( 0.23 % ) , all matched for an apparent viscosity of 61 mPa·s at 50 s−1 , as well as dairy-based beverages and puddings with 0 % or 1 % soluble fiber added . Blood sample s were collected at fasting and up to 2 hours postpr and ially for determination of glucose and insulin concentrations . Area under the curve ( AUC ) , peak concentration , and time-to-peak values as well as glycemic index ( GI ) and insulinemic index ( II ) were calculated . Results : Fiber fortification of a 50 g glucose solution had no effect on postpr and ial blood glucose or insulin levels , even at a high concentration ( i.e. , 6 % soy-soluble polysaccharides ) . Glucose AUC and GI values for the dairy-based beverage ( p < 0.05 ) and pudding ( p < 0.01 ) controls were significantly lower than the glucose reference . Glucose AUC and GI values for the soy-soluble polysaccharide-fortified dairy products ( p < 0.01 ) and flaxseed gum – fortified dairy products ( p < 0.001 ) were significantly lower than the glucose reference . No significant differences were observed between the fiber-fortified fluid and gelled dairy-based study treatments and no significant differences were observed in terms of the insulin AUC , II , and peak insulin concentration between any of the dairy products . Conclusions : All dairy products had lower glycemic responses relative to the reference , with no effect of beverage versus pudding matrix observed and minimal impact of 1 % flaxseed gum or soy-soluble polysaccharides . Product apparent viscosity , but not fiber concentration , was significantly and inversely correlated with glucose AUC and GI The gut microbiota has been implicated in obesity and its progression towards metabolic disease . Dietary interventions that target the gut microbiota have been suggested to improve metabolic health . The aim of the present study was to investigate the effect of interventions with Lactobacillus paracasei F19 or flaxseed mucilage on the gut microbiota and metabolic risk markers in obesity . A total of fifty-eight obese postmenopausal women were r and omised to a single-blinded , parallel-group intervention of 6-week duration , with a daily intake of either L. paracasei F19 ( 9·4 × 1010 colony-forming units ) , flaxseed mucilage ( 10 g ) or placebo . Quantitative metagenomic analysis of faecal DNA was performed to identify the changes in the gut microbiota . Diet-induced changes in metabolic markers were explored using adjusted linear regression models . The intake of flaxseed mucilage over 6 weeks led to a reduction in serum C-peptide and insulin release during an oral glucose tolerance test ( P < 0·05 ) and improved insulin sensitivity measured by Matsuda index ( P < 0·05 ) . Comparison of gut microbiota composition at baseline and after 6 weeks of intervention with flaxseed mucilage  showed alterations in abundance of thirty-three metagenomic species ( P < 0·01 ) , including decreased relative abundance of eight Faecalibacterium species . These changes in the microbiota could not explain the effect of flaxseed mucilage on insulin sensitivity . The intake of L. paracasei F19 did not modulate metabolic markers compared with placebo . In conclusion , flaxseed mucilage  improves insulin sensitivity and alters the gut microbiota ; however , the improvement in insulin sensitivity was not mediated by the observed changes in relative abundance of bacterial species Although high alpha-linolenic acid flaxseed ( Linum usitatissimum ) is one of the richest dietary sources of alpha-linolenic acid and is also a good source of soluble fibre mucilage , it is relatively unstudied in human nutrition . Healthy female volunteers consumed 50 g ground , raw flaxseed/d for 4 weeks which provided 12 - 13 % of energy intake ( 24 - 25 g/100 g total fat ) . Flaxseed raised alpha-linolenic acid and long-chain n-3 fatty acids in both plasma and erythrocyte lipids , as well as raising urinary thiocyanate excretion 2.2-fold . Flaxseed also lowered serum total cholesterol by 9 % and low-density-lipoprotein-cholesterol by 18 % . Changes in plasma alpha-linolenic acid were equivalent when 12 g alpha-linolenic acid/d was provided as raw flaxseed flour ( 50 g/d ) or flaxseed oil ( 20 g/d ) suggesting high bioavailability of alpha-linolenic acid from ground flaxseed . Test meals containing 50 g carbohydrate from flaxseed or 25 g flaxseed mucilage each significantly decreased postpr and ial blood glucose responses by 27 % . Malondialdehyde levels in muffins containing 15 g flaxseed oil or flour/kg were similar to those in wheat-flour muffins . Cyanogenic glycosides ( linamarin , linustatin , neolinustatin ) were highest in extracted flaxseed mucilage but were not detected in baked muffins containing 150 g flaxseed/kg . We conclude that up to 50 g high-alpha-linolenic acid flaxseed/d is palatable , safe and may be nutritionally beneficial in humans by raising n-3 fatty acids in plasma and erythrocytes and by decreasing postpr and ial glucose responses Dietary estrogens , such as lignans , are similar in structure to endogenous sex steroid hormones and may act in vivo to alter hormone metabolism and subsequent cancer risk . The objective of this study was to examine the effect of dietary intake of a lignan-rich plant food ( flaxseed ) on urinary lignan excretion in postmenopausal women . This r and omized , cross-over trial consisted of three 7-week feeding periods during which 31 healthy postmenopausal women , ages 52 - 82 years , consumed their habitual diets plus 0 , 5 , or 10 grams of ground flaxseed per day . Urine sample s collected for 2 consecutive days during the last week of each feeding period were analyzed for lignan content ( enterodiol , enterolactone , and matairesinol ) by isotope dilution gas chromatography/mass spectrometry . Compared with the 0-gram flaxseed diet , consumption of 5 or 10 grams of flaxseed significantly increased excretion of enterodiol by 1,009 and 2,867 nmol/day , respectively ; significantly increased excretion of enterolactone by 21,242 and 52,826 nmol/day , respectively ; and significantly increased excretion of total lignans ( enterodiol + enterolactone + matairesinol ) by 24,333 and 60,640 nmol/day , respectively . Excretion of matairesinol was not significantly altered by flaxseed consumption . Consumption of flax , a significant source of dietary estrogens , in addition to their habitual diets increased excretion of enterodiol and enterolactone , but not matairesinol , in a dose-dependent manner in this group of postmenopausal women .  Urinary excretion of lignan metabolites is a dose-dependent biomarker of flaxseed intake within the context of a habitual diet Background Obesity leads to an increase in inflammation and insulin resistance . This study determined antioxidant activity of flaxseed and its role in inflammation and insulin resistance in obese glucose intolerant people . Methods Using a r and omized crossover design , nine obese glucose intolerant people consumed 40 g ground flaxseed or 40 g wheat bran daily for 12 weeks with a 4-week washout period . Plasma inflammation biomarkers ( CRP , TNF-α , and IL-6 ) , glucose , insulin , and thiobaribituric acid reactive substance ( TBARS ) were measured before and after of each supplementation . Results Flaxseed supplementation  decreased TBARS ( p = 0.0215 ) and HOMA-IR ( p = 0.0382 ) . Flaxseed or wheat bran supplementation did not change plasma inflammatory biomarkers . A positive relationship was found between TBARS and HOMA-IR ( r = 0.62 , p = 0.0003 ) . Conclusions The results of the study weakly support that decreased insulin resistance might have been secondary to antioxidant activity of flaxseed . However , the mechanism(s ) of decreased insulin resistance by flaxseed should be further determined using flaxseed lignan OBJECTIVE Due to its high content of lignans , alpha-linolenic acid and fiber , flaxseed may reduce cardiovascular disease risk in humans . The present study evaluated the effect of flaxseed on markers of cardiovascular disease risk in healthy menopausal women . METHODS One hundred ninety-nine women were r and omly assigned to consume 40 g daily of flaxseed or wheat germ placebo for 12 mo . Fatty acids , apolipoproteins A-1 and B , lipoprotein(a ) , low-density lipoprotein particle size , fibrinogen , C-reactive protein , insulin , and glucose were measured at baseline and at 12 mo . RESULTS In total 179 women were available for the intention-to-treat analysis .  Flaxseed increased plasma alpha-linolenic ( P < 0.0001 ) , docosapentaenoic ( P = 0.001 ) , and total omega-3 fatty ( P = 0.0004 ) acids . Differences between flaxseed and wheat germ were observed for apolipoprotein A-1 ( -0.10 + /- 0.26 g/L , P = 0.011 ) and apolipoprotein B ( -0.05 + /- 0.16 g/L , P = 0.047 ) . From baseline , flaxseed raised apolipoproteins A-1 and B by 4.4 % ( P = 0.006 ) and 3 % ( P = 0.054 ) , whereas wheat germ increased these apolipoproteins by 11.6 % ( P < 0.0001 ) and 7 % ( P = 0.0001 ) , respectively . Both treatments increased lipoprotein(a ) ( P < 0.0001 ) and decreased low-density lipoprotein peak particle size ( P < 0.0001 ) . CONCLUSION In this large , long-term , placebo-controlled trial in healthy menopausal women , flaxseed increased some omega-3 fatty acids in plasma and had a limited effect on apolipoprotein metabolism Inflammation and lipid abnormalities are two important risk factors for cardiovascular disease in hemodialysis ( HD ) patients . The present study was design ed to investigate the effects of flaxseed consumption on systemic inflammation and serum lipid profile in HD patients with lipid abnormalities . This was an unblinded , r and omized clinical trial . Thirty HD patients with dyslipidemia ( triglyceride > 200 mg/dL and /or high‐density lipoprotein‐cholesterol ( HDL‐C ) < 40 mg/dL ) were r and omly assigned to either a flaxseed or control group . Patients in the flaxseed group received 40 g/day ground flaxseed for 8 weeks , whereas patients in the control group received their usual diet , without any flaxseed . At baseline and at the end of week 8 , 7 mL of blood was collected after a 12‐ to 14‐hour fast and serum concentrations of triglyceride , total cholesterol , low‐density lipoprotein‐cholesterol ( LDL‐C ) , HDL‐C , and C‐reactive protein ( CRP ) were measured . Serum concentrations of triglyceride ( P < 0.01 ) , total cholesterol ( P < 0.01 ) , LDL‐C ( P < 0.01 ) , and CRP ( P < 0.05 ) decreased significantly in the flaxseed group at the end of week 8 compared with baseline , whereas serum HDL‐C showed a significant increase ( P < 0.01 ) . These changes in the flaxseed group were significant in comparison with the control group . The study indicates that flaxseed consumption improves lipid abnormalities and reduces systemic inflammation in HD patients with lipid abnormalities Purpose The aim of this study was to investigate the effects of flaxseed oil consumption on serum systemic and vascular inflammation markers , and oxidative stress in hemodialysis ( HD ) patients . Methods In this r and omized , double-blind , clinical trial , 34 HD patients were r and omly assigned to either the flaxseed oil or the control group . The patients in the flaxseed oil group received 6 g/day flaxseed oil for 8 week , whereas the control group received 6 g/day medium-chain triglycerides ( MCT ) oil . At baseline and the end of week 8 , serum concentrations of high-sensitive C-reactive protein ( hs-CRP ) , soluble intercellular adhesion molecule type 1 ( sICAM-1 ) , soluble vascular cell adhesion molecule type 1 ( sVCAM-1 ) , sE-selectin , and malondialdehyde ( MDA ) were measured after a 12- to 14-h fast . Results Serum hs-CRP , a systemic inflammation marker , and sVCAM-1 , a vascular inflammation marker , reduced significantly in the flaxseed oil group at the end of week 8 compared to baseline ( P < 0.05 ) , and the reductions were significant in comparison with the MCT oil group ( P < 0.05 ) . There were no significant differences between the two groups in mean changes in serum sICAM-1 , sE-selectin , and MDA . Conclusion This study indicates that daily consumption of 6 g flaxseed oil reduces serum hs-CRP and sVCAM-1 , which are two risk factors for CVD . Therefore , the inclusion of flaxseed oil in the usual diet of HD patients can be considered as a strategy for reducing CVD risk factors Objective : Flaxseed is a rich source of alpha linolenic acid ( ALA ) , fiber and lignans , making it a potentially attractive functional food for modulating cardiovascular risk . We studied the effects of flaxseed on markers of cardiovascular risk in hypercholesterolemic adults . Methods : Sixty-two men and post-menopausal women with pre- study low density lipoprotein cholesterol ( LDL-C ) between 130 and 200 mg/dl were r and omized to 40g/day of ground flaxseed-containing baked products or matching wheat bran products for 10 weeks while following a low fat , low cholesterol diet .  Fasting lipoproteins , measures of insulin resistance , inflammation , oxidative stress , and safety were assessed at 0 , 5 and 10 weeks . Results : Flaxseed was well-tolerated , and increased serum levels of ALA ( p < 0.001 ) . Compared to wheat , flaxseed significantly reduced LDL-C at 5 weeks ( −13 % , p < 0.005 ) , but not at 10 weeks ( −7 % , p = 0.07 ) . Flaxseed  reduced lipoprotein a ( Lp[a ] ) by a net of 14 % ( p = 0.02 ) , and reduced the homeostatic model assessment of insulin resistance ( HOMA-IR ) index by 23.7 % ( p = 0.03 ) compared to wheat at 10 weeks , but did not affect markers of inflammation ( IL-6 , Hs-CRP ) or oxidative stress ( ox LDL , urinary isoprostanes ) at any time points . In men , flaxseed  reduced HDL-C concentrations by a net of 16 % ( p = 0.03 ) and 9 % ( p = 0.05 ) at 5 and 10 weeks , respectively . Conclusions : Ground flaxseed has a modest but short lived LDL-C lowering effect , yet reduces Lp(a ) and improves insulin sensitivity in hyperlipidemic adults . The HDL-C lowering effect of flaxseed in men warrants additional study BACKGROUND Flaxseed is a promising alternative to reduce the risk of diseases associated with body weight excess because it is rich in a-linolenic acid , lignans , and dietary fiber . Flaxseed ( Linum usitatissimum ) can be found in brown and golden varieties ; however , questions have arisen as to whether the variety may influence the health effects . OBJECTIVE The objective of this study was to compare the effects of brown and golden flaxseeds on lipid profile , glycemia , blood pressure , inflammatory status , body weight , and body composition in overweight adolescents . METHODS Seventy-five overweight adolescents ( 33 boys , 42 girls ; age 13.7 ! 2.1 y ) , from Alegre-ES , Brazil , were r and omized to one of the three groups ( n ¼ 25 ) on a parallel , single-blind clinical trial . They received 28 g/d of brown flaxseed ( BF ) , golden flaxseed ( GF ) , or the equivalent amount of wheat bran ( Control , CG ) in different preparations at school from Monday to Friday for 11 wk . Blood pressure , anthropometric evaluation , and the analyses of blood total cholesterol , lipoproteins , glucose , and inflammatory markers were performed at the beginning and at the end of the intervention . The data were analyzed by ANCOVA at 5 % significance . RESULTS The groups who consumed brown and golden flaxseed showed significant reduction in diastolic blood pressure . Brown and golden flaxseed did not differentially affect plasma lipid responses , plasma glucose and inflammatory profile , although all groups ( BF , GF , and CG ) showed increased levels of TNF-a . CONCLUSIONS The adolescents consumed about half the daily amount provided , which may not have been sufficient to exert the health benefits of flaxseed reported in the literature , concerning the lipid profile , inflammation biomarkers and body composition Background Flaxseed has received attention for its anti-inflammatory and antioxidant role . The present study hypothesizes if flaxseed added to a weight loss diet could improve the lipid and metabolic profiles and decrease risk factors related to cardiovascular disease . Methods In a prospect i ve , single blinded 42 days protocol , subjects were allocated into two groups with low carbohydrates intake : GriceLC ( 35 % of carbohydrate and 60 g of raw rice powder per day ) and GflaxLC ( 32 % of carbohydrate and 60 g of flaxseed powder per day ) . Blood pressure , anthropometric measures and serum levels of isoprostane , C-reactive protein , Tumor Necrosis Factor-alpha , glucose , lipidic profile , uric acid , adiponectin , leptin and insulin were measured at baseline and at the end of interventions . Serum and urinary enterodiol and enterolactione were also measured . Results A total of 27 men with cardiovascular risk factors were evaluated , with mean age of 33 ± 10 years to GriceLC and 40 ± 9 years to GflaxLC . Both groups experienced weight loss and systolic blood pressure reduction . A decrease in inflammatory markers ( CRP and TNF-α ) was observed after flaxseed intake ( mean decrease of 25 % and 46 % for GflaxLC respectively ) . All groups also showed improvement in levels of total cholesterol , LDL-c , uric acid and adiponectin . Only GflaxLC group showed a decrease in triglyceride levels . Conclusion This study suggests that flaxseed added to a weight loss diet could be an important nutritional strategy to reduce inflammation markers such as CRP and TNF-α . Trial registration Clinical Trials.gov NCT02132728 Flaxseed is one of the richest sources of lignans and is increasingly used in food products or as a supplement . Plant lignans can be converted by intestinal bacteria into the so-called enterolignans , enterodiol and enterolactone . For a proper evaluation of potential health effects of enterolignans , information on their bioavailability is essential . The aim of this study was to investigate whether crushing and milling of flaxseed enhances the bioavailability of enterolignans in plasma . In a r and omized , crossover study , 12 healthy subjects supplemented their diet with 0.3 g whole , crushed , or ground flaxseed/(kg body weight . d ) . Each subject consumed flaxseed for 10 successive days separated by 11-d run-in/wash-out periods , in which the subjects consumed a diet poor in lignans . Blood sample s were collected at the end of each run-in/wash-out period , and at the end of each supplement period . Plasma enterodiol and enterolactone were measured using LC-MS-MS . The mean relative bioavailability of enterolignans from whole compared with ground flaxseed was 28 % ( P < or = 0.01 ) , whereas that of crushed compared with ground flaxseed was 43 % ( P < or = 0.01 ) . Crushing and milling of flaxseed substantially improve the bioavailability of the enterolignans Background : Prostate cancer affects one of six men during their lifetime . Dietary factors are postulated to influence the development and progression of prostate cancer . Low-fat diets and flaxseed supplementation may offer potentially protective strategies . Methods : We undertook a multisite , r and omized controlled trial to test the effects of low-fat and /or flaxseed-supplemented diets on the biology of the prostate and other biomarkers . Prostate cancer patients ( n = 161 ) scheduled at least 21 days before prostatectomy were r and omly assigned to one of the following arms : ( a ) control ( usual diet ) , ( b ) flaxseed-supplemented diet ( 30 g/d ) , ( c ) low-fat diet ( < 20 % total energy ) , or ( d ) flaxseed-supplemented , low-fat diet . Blood was drawn at baseline and before surgery and analyzed for prostate-specific antigen , sex hormone-binding globulin , testosterone , insulin-like growth factor-I and binding protein-3 , C-reactive protein , and total and low-density lipoprotein cholesterol . Tumors were assessed for proliferation ( Ki-67 , the primary endpoint ) and apoptosis . Results : Men were on protocol an average of 30 days . Proliferation rates were significantly lower ( P < 0.002 ) among men assigned to the flaxseed arms . Median Ki-67-positive cells/total nuclei ratios ( ×100 ) were 1.66 ( flaxseed-supplemented diet ) and 1.50 ( flaxseed-supplemented , low-fat diet ) versus 3.23 ( control ) and 2.56 ( low-fat diet ) . No differences were observed between arms with regard to side effects , apoptosis , and most serologic endpoints ; however , men on low-fat diets experienced significant decreases in serum cholesterol ( P = 0.048 ) . Conclusions : Findings suggest that flaxseed is safe and associated with biological alterations that may be protective for prostate cancer . Data also further support low-fat diets to manage serum cholesterol . ( Cancer Epidemiol Biomarkers Prev 2008;17(12):3577–87 Abstract Context : The natural health product , BeneFlax , is a st and ardized flaxseed [ Linum usitatissimum L. ( Linaceae ) ] lignan enriched product with evidence of product quality and known quantity of the bioactive component , lignan . The acceptance of this natural health product for its various health benefits requires greater evidence of its safety in the general population . Objective : We determined whether flaxseed lignan causes clinical hypoglycemia or hypotension in healthy older adults as an important aspect of safety . Material s and methods : Participants aged 49–87 years were r and omized in a double-blind trial to receive flaxseed lignan ( 543 mg/day in BeneFlax ) or placebo while completing a 6-month walking program . The 94 participants who completed the study were stratified by age ( < 65 years versus ≥65 years ) and treatment category to determine whether older adults were more susceptible to adverse effects . Results : After 6 months of treatment , average plasma glucose level ( 5.4 ± 0.6 mmol/L ) , systolic blood pressure ( 127 ± 14 mm Hg ) , and diastolic blood pressure ( 80 ± 9 mm Hg ) were within normal clinical range . Controlling for sex and body mass index covariates result ed in no observed differences between plasma glucose or blood pressure measurements between treatment or age groups ( p > 0.05 ) . No incidents of hypoglycemia or hypotension were observed during BeneFlax treatment , suggesting that 543 mg falls at or below the no observable adverse effect level ( NOAEL ) . Discussion and conclusion : These data suggest the flaxseed lignan product BeneFlax does not pose a risk of hypoglycemia or hypotension in healthy adults aged 49–87 years OBJECTIVE Animal studies have demonstrated that dietary supplementation with flaxseed oil inhibits colorectal cancer growth . Recent data indicate that walnuts have strong antiproliferative properties against colon cancer cells in vitro but no previous study has assessed the effects of walnuts in vivo or performed a joint evaluation of flaxseed oil and walnuts . The aim of the present study was to examine the effect of dietary walnuts on colorectal cancer in vivo and to comparatively evaluate their efficacy in relation to flaxseed oil . METHODS HT-29 human colon cancer cells were injected in 6-wk-old female nude mice . After a 1-wk acclimation period , mice ( n = 48 ) were r and omized to diets containing ∼19 % of total energy from walnuts , flaxseed oil , or corn oil ( control ) and were subsequently studied for 25 d. RESULTS Tumor growth rate was significantly slower in walnut-fed and flaxseed-fed mice compared with corn oil-fed animals ( P < 0.05 ) by 27 % and 43 % , respectively . Accordingly , final tumor weight was reduced by 33 % and 44 % , respectively ( P < 0.05 versus control ) ; the differences between walnut and flaxseed diets did not reach significance . We found no differences among groups in metabolic and hormonal profile , serum antioxidant capacity , or inflammation ( P > 0.05 ) . However , walnuts and flaxseed oil significantly reduced serum expression levels of angiogenesis factors , including vascular endothelial growth factor ( by 30 % and 80 % , respectively ) , and approximately doubled total necrotic areas despite smaller tumor sizes ( P < 0.05 versus control ) . Dietary walnuts significantly decreased angiogenesis ( CD34 staining ; P = 0.017 versus control ) , whereas this effect did not reach significance in the flaxseed oil group ( P = 0.454 versus control ) . CONCLUSION We conclude that walnuts in the diet inhibit colorectal cancer growth by suppressing angiogenesis . Further studies are needed to confirm our findings in humans and explore underlying mechanisms The objective of this study was to evaluate the efficacy of flaxseed meal and flaxseed extract in reducing climacteric symptoms of menopausal women . Ninety menopausal women were r and omly distributed into three study groups : group I received 1 g per day of flaxseed extract containing at least 100 mg of secoisolariciresinol diglucoside ( SDG ) , group II received 90 g per day of flaxseed meal containing at least 270 mg of SDG , and group III received 1 g per day of collagen ( placebo group ) . Subjects were assessed for menopausal symptoms by the Kupperman index at the beginning and at the end of the 6 months of treatment . Subjects were also assessed for endometrial thickness and vaginal cytology . The Kupperman index values at the beginning and end of the treatments were analyzed using the paired t-test . Both the flaxseed extract ( P=.007 ) and the flaxseed meal ( P=.005 ) were effective in reducing the menopausal symptoms when compared with the placebo control ( P=.082 ) . Alternatively , the changes in Kupperman index were also computed and su bmi tted to analysis of variance . In this case , no significant differences were found ( P=.084 ) although the data indicate a decreasing tendency for the Kupperman index by both the flaxseed extract and the flaxseed meal groups . Neither the flaxseed extract nor the flaxseed meal exerted clinical ly important estrogenic effects on the vaginal epithelium or endometrium as revealed by the absence of changes in the blood levels of follicle stimulating hormone and estradiol , as well as in the endometrial thickness , and vaginal epithelial maturation value . No serious adverse events related to the treatments were reported . Although the results of the present study do not allow an unequivocal conclusion about the action of flaxseed on the menopausal symptoms , they suggest that it could be premature to conclude that no such action exists . Clearly the matter still deserves further experimental attention BACKGROUND Currently there is considerable interest in the potential health benefits of oil seeds , such as soy and flaxseed , especially in relation to cardiovascular disease and cancer . OBJECTIVE We therefore evaluated health aspects of partially defatted flaxseed in relation to serum lipids , indicators of oxidative stress , and ex vivo sex hormone activities . DESIGN Twenty-nine hyperlipidemic subjects ( 22 men and 7 postmenopausal women ) completed two 3-wk treatment periods in a r and omized , crossover trial . Subjects were given muffins that contributed approximately 20 g fiber/d from either flaxseed ( approximately 50 g partially defatted flaxseed/d ) or wheat bran ( control ) while they consumed self-selected National Cholesterol Education Program Step II diets . Both muffins had similar macronutrient profiles . Treatment phases were separated by > or = 2 wk . RESULTS Partially defatted flaxseed reduced total cholesterol ( 4.6+/-1.2 % ; P = 0.001 ) , LDL cholesterol ( 7.6+/-1.8 % ; P < 0.001 ) , apolipoprotein B ( 5.4+/-1.4 % ; P = 0.001 ) , and apolipoprotein A-I ( 5.8+/-1.9 % ; P = 0.005 ) , but had no effect on serum lipoprotein ratios at week 3 compared with the control . There were no significant effects on serum HDL cholesterol , serum protein carbonyl content , or ex vivo and rogen or progestin activity after either treatment . Unexpectedly , serum protein thiol groups were significantly lower ( 10.8+/-3.6 % ; P = 0.007 ) at week 3 after the flaxseed treatment than after the control , suggesting increased oxidation . CONCLUSIONS These data indicate that partially defatted flaxseed is effective in lowering LDL cholesterol . No effects on lipoprotein ratios , ex vivo serum and rogen or progestin activity , or protein carbonyl content were observed . The significance of increased oxidation of protein thiol groups with flaxseed consumption requires further investigation SCOPE To investigate the effects of n-3 fatty acid supplements , both marine and plant-based , on glycemic traits in Chinese type 2 diabetes patients . METHOD AND RESULTS In a double-blind r and omized controlled trial , 185 recruited Chinese type 2 diabetes patients were r and omized to either fish oil ( FO , n = 63 ) , flaxseed oil ( FSO , n = 61 ) , or corn oil group ( served as control group , n = 61 ) for 180 days . The patients were asked to take corresponding oil capsules ( four capsules/day ) , which totally provided 2 g/day of eicosapentaenoic acid + docosahexaenoic acid in FO group and 2.5 g/day of alpha-linolenic acid in FSO group . No group × time interaction was observed for homeostatic model assessment of insulin resistance , fasting insulin , or glucose . Significant group × time interaction ( P = 0.035 ) was observed for glycated hemoglobin A1c ( HbA1c ) , with HbA1c decreased in FO group compared with corn oil group ( P = 0.037 ) . We also found significant group × time interactions for lipid traits , including LDL cholesterol ( P = 0.043 ) , total cholesterol ( P = 0.021 ) , total cholesterol/HDL cholesterol ( P = 0.009 ) , and triacylglycerol ( P = 0.003 ) , with the lipid profiles improved in FO group . No significant effects of FSO on glycemic traits or blood lipids were observed . CONCLUSIONS Marine n-3 PUFA supplements may improve glycemic control and lipid profiles among Chinese type 2 diabetic patients BACKGROUND Dietary flaxseed lowers cholesterol in healthy subjects with mild biomarkers of cardiovascular disease ( CVD ) . OBJECTIVE The aim was to investigate the effects of dietary flaxseed on plasma cholesterol in a patient population with clinical ly significant CVD and in those administered cholesterol-lowering medications ( CLMs ) , primarily statins . METHODS This double-blind , r and omized , placebo-controlled trial examined the effects of a diet supplemented for 12 mo with foods that contained either 30 g of milled flaxseed [ milled flaxseed treatment ( FX ) group ; n = 58 ] or 30 g of whole wheat [ placebo ( PL ) group ; n = 52 ] in a patient population with peripheral artery disease ( PAD ) .  Plasma lipids were measured at 0 , 1 , 6 , and 12 mo . RESULTS Dietary flaxseed in PAD patients result ed in a 15 % reduction in circulating LDL cholesterol as early as 1 mo into the trial ( P = 0.05 ) . The concentration in the FX group ( 2.1 ± 0.10 mmol/L ) tended to be less than in the PL group ( 2.5 ± 0.2 mmol/L ) at 6 mo ( P = 0.12 ) , but not at 12 mo ( P = 0.33 ) . Total cholesterol also tended to be lower in the FX group than in the PL group at 1 mo ( 11 % , P = 0.05 ) and 6 mo ( 11 % , P = 0.07 ) , but not at 12 mo ( P = 0.24 ) . In a subgroup of patients taking flaxseed and CLM ( n = 36 ) , LDL-cholesterol concentrations were lowered by 8.5 % ± 3.0 % compared with baseline after 12 mo . This differed from the PL + CLM subgroup ( n = 26 ) , which increased by 3.0 % ± 4.4 % ( P = 0.030 ) to a final concentration of 2.2 ± 0.1 mmol/L. CONCLUSIONS Milled flaxseed lowers total and LDL cholesterol in patients with PAD and has additional LDL-cholesterol-lowering capabilities when used in conjunction with CLMs . This trial was registered at clinical trials.gov as NCT00781950 Lignans , derived from flaxseed , are phyto-oestrogens being increasingly studied for their health benefits . An 8-week , r and omised , double-blind , placebo-controlled study was conducted in fifty-five hypercholesterolaemic subjects , using treatments of 0 ( placebo ) , 300 or 600 mg/d of dietary secoisolariciresinol diglucoside ( SDG ) from flaxseed extract to determine the effect on plasma lipids and fasting glucose levels . Significant treatment effects were achieved ( P < 0.05 to < 0.001 ) for the decrease of total cholesterol ( TC ) , LDL-cholesterol ( LDL-C ) and glucose concentrations , as well as their percentage decrease from baseline . At weeks 6 and 8 in the 600 mg SDG group , the decreases of TC and LDL-C concentrations were in the range from 22.0 to 24.38 % respectively ( all P < 0.005 compared with placebo ) . For the 300 mg SDG group , only significant differences from baseline were observed for decreases of TC and LDL-C. A substantial effect on lowering concentrations of fasting plasma glucose was also noted in the 600 mg SDG group at weeks 6 and 8 , especially in the subjects with baseline glucose concentrations > or = 5.83 mmol/l ( lowered 25.56 and 24.96 % ; P = 0.015 and P = 0.012 compared with placebo , respectively ) . Plasma concentrations of secoisolariciresinol ( SECO ) , enterodiol ( ED ) and enterolactone were all significantly raised in the groups supplemented with flaxseed lignan . The observed cholesterol-lowering values were correlated with the concentrations of plasma SECO and ED ( r 0.128 - 0.302 ; P < 0.05 to < 0.001 ) . In conclusion , dietary flaxseed lignan extract decreased plasma cholesterol and glucose concentrations in a dose-dependent manner BACKGROUND Botanical omega-3 fatty acid ( alphalinolenic acid/ALA ) has been shown to alleviate the prothrombotic and proinflammatory profile of metabolic syndrome , however clinical protocol s are still scarce . Aim ing to focus an obese population , a pilot study was design ed . METHODS Morbidly obese c and i date s for bariatric surgery ( n = 29 , age 46.3 ± 5.2 years ) , 82.8 % females ( 24/29 ) , BMI 44.9 ± 5.2 kg/m² , with C-reactive protein/CRP > 5 mg/L were recruited . Twenty were r and omized and after exclusions , 16 were available for analysis . Flaxseed powder ( 60 g/day , 10 g ALA ) and isocaloric roasted cassava powder ( 60 g/day , fat-free ) were administered in a double-blind routine for 12 weeks . RESULTS During flaxseed consumption neutrophil count decreased and fibrinogen , complement C4 , prothrombin time and carotid diameter remained stable , whereas placebo ( cassava powder ) was associated with further elevation of those measurements . CONCLUSIONS Inflammatory and coagulatory markers tended to exhibit a better outlook in the flaxseed group . Also large-artery diameter stabilized whereas further increase was noticed in controls . These findings raise the hypothesis of a less deleterious cardiovascular course in seriously obese subjects receiving a flaxseed supplement Summary Background Both hempseed oil ( HO ) and flaxseed oil ( FO ) contain high amounts of essential fatty acids ( FAs ) ; i.e. linoleic acid ( LA , 18:2n-6 ) and alpha-linolenic acid ( ALA , 18:3n-3 ) , but almost in opposite ratios . An excessive intake of one essential FA over the other may interfere with the metabolism of the other while the metabolisms of LA and ALA compete for the same enzymes . It is not known whether there is a difference between n-3 and n-6 FA of plant origin in the effects on serum lipid profile . Aim of the study To compare the effects of HO and FO on the profile of serum lipids and fasting concentrations of serum total and lipoprotein lipids , plasma glucose and insulin , and haemostatic factors in healthy humans . Methods Fourteen healthy volunteers participated in the study . A r and omised , double-blind crossover design was used . The volunteers consumed HO and FO ( 30 ml/day ) for 4 weeks each . The periods were separated by a 4-week washout period . Results The HO period result ed in higher proportions of both LA and gamma-linolenic acid in serum cholesteryl esters ( CE ) and triglycerides ( TG ) as compared with the FO period ( P < 0.001 ) , whereas the FO period result ed in a higher proportion of ALA in both serum CE and TG as compared with the HO period ( P < 0.001 ) . The proportion of arachidonic acid in CE was lower after the FO period than after the HO period ( P < 0.05 ) . The HO period result ed in a lower total-to-HDL cholesterol ratio compared with the FO period ( P = 0.065 ) . No significant differences were found between the periods in measured values of fasting serum total or lipoprotein lipids , plasma glucose , insulin or hemostatic factors . Conclusions The effects of HO and FO on the profile of serum lipids differed significantly , with only minor effects on concentrations of fasting serum total or lipoprotein lipids , and no significant changes in concentrations of plasma glucose or insulin or in haemostatic factors
Conclusions Whole flaxseed , but not flaxseed oil and lignan extract , has significant effects on improving glycemic control .
Context The results of human clinical trials investigating the effects of flaxseed on glucose control and insulin sensitivity are inconsistent .
Objective The present study aim ed to systematic ally review and analyze r and omized controlled trials assessing the effects of flaxseed consumption on glycemic control .