In memory of Dr Johanna Budwig 1908 – 2003

Flax, Flaxseed, Flaxseed Oil – A selection of Scientific Studies :

Cardio

Dietary Flaxseed Reduces Central Aortic Blood Pressure Without Cardiac Involvement but Through Changes in Plasma Oxylipins.

Abstract

In the year-long FlaxPAD clinical trial (Flaxseed for Peripheral Artery Disease), dietary flaxseed generated a powerful reduction in brachial systolic and diastolic blood pressure in patients with peripheral artery disease. Oxylipins were implicated as potential mechanistic mediators. However, the ability of flaxseed to impact central aortic hypertension, arterial stiffness, or cardiac performance was not investigated. Additionally, the relationship between central blood pressure (cBP) and oxylipins was not elucidated. Therefore, radial tonometry and pulse wave analysis were used to measure cBP and cardiac function in the FlaxPAD population (n=62). Plasma oxylipins were analyzed with high-performance liquid chromatography mass spectrometry. In patients with high blood pressure at baseline, the average decrease in central systolic and diastolic blood pressures versus placebo was 10 and 6 mm Hg, respectively. Flaxseed did not significantly impact augmentation index or other cardiac function indices. Alternatively, the data support several specific oxylipins as potential mediators in the antihypertensive properties of flaxseed. For example, every 1 nmol/L increase in plasma 16-hydroxyeicosatetraenoic acid increased the odds of higher central systolic and diastolic blood pressures by 12- and 9-fold, respectively. Every 1 nmol/L increase in plasma thromboxane B2 and 5,6-dihydroxyeicosatrienoic acid increased the odds of higher cBP by 33- and 9-fold, respectively. Flaxseed induced a decrease in many oxylipins, which corresponded with a reduced risk of elevated cBP. These data extend the antihypertensive properties of flaxseed to cBP without cardiac involvement but rather through oxylipins.

This study provides further support for oxylipins as therapeutic targets in hypertension.

KEYWORDS:

central blood pressure; flaxseed; hypertension; nutrition; oxylipins; peripheral vascular disease; pulse wave analysis

PMID : 27528063

 

Impact of dietary flaxseed (linum usitatissimum) supplementation on biochemical profile in healthy rats.

Abstract

Flaxseed has been suggested play preventive and therapeutic roles in cardiovascular disease. The aim of this study was to evaluate the influence of flaxseed-supplemented dietary in healthy rats. We used 30 rats divided in three groups (n = 10): Control Group (C) was fed with a casein-based chow (10% protein; 5% fiber; 7% lipid); Flaxseed Group (F) was fed with the casein-based chow supplemented with 25% flaxseed (10% protein; 7% fiber; 11% lipid); Internal Control Group (IC) was fed with the casein-based chow plus soybean oil and fiber (10% protein; 7% fiber; 11% lipid). The blood was obtained by cardiac puncture (after 180 days) and the serum was separated for lipid profile, glucose and uric acid analyses by commercial kit. Although all groups fed the same amount of ration, F group presented low (p < 0.05) body mass than C and IC groups. Total cholesterol and triacylgycerol were similar between all groups. F group presented HDL-C (High-density lipoprotein cholesterol) increase (p < 0.05) in 47% when compared C group. The LDL-C (Low-density lipoprotein cholesterol), glucose and uric acid were reduced (p < 0.05) 22%, 78% 64%, respectively, in F compared to C group.

All results together suggest that the supplementation with 20% o flaxseed might be important to prevent cardiovascular disorders.

PMID : 22470026

 

 

Overview of Flaxseed Patent Applications for the Reduction of Cholesterol Levels.

Abstract

BACKGROUND:

Flaxseed is becoming an increasingly widely used food ingredient. The rising interest of the food industry in this nutraceutical is primarily because of functional nutrients, such as alpha-linolenic acid and lignans, which have health benefits due to their lipid-lowering properties.

OBJECTIVE:

The objective of this study was to provide an overview of the patenting of flaxseed products with cholesterol-lowering effects.

METHOD:

Patent applications filed by country of origin were retrieved from the Derwent Innovations Index®database.

RESULTS:

A total of 307 patent documents were identified, of which 184 claim the use of flaxseed or parts of the flax plant in the product formulation, for their lipid-lowering effect when consumed by humans. A few of the patent applications contain claims for new products based on flaxseed in isolation, including the preparation of foods designed to inhibit the production of cholesterol. Most of the claims were for flaxseed in the form of oil and in association with other lipid-lowering compounds, mainly for the food industry, in the form of dietary supplements or baked products designed to raise their high-density lipoprotein content, and for treating heart problems. China and the United States are the leading countries of flax-related applications.

CONCLUSION:

These results may have important implications for the production of functional food products that meet specific societal demands.

KEYWORDS:

Cholesterol; flaxseed; flaxseed products; functional food; linseed; nutraceuticals; patent

PMID: 26996439

Omega-3-fatty acid adds to the protective effect of flax lignan concentrate in pressure overload-induced myocardial hypertrophy in rats via modulation of oxidative stress and apoptosis.

Abstract

Objective of the present investigation was to study the effect of the flax lignan concentrate (FLC) and Omega-3-fatty acid (O-3-FA) on myocardial apoptosis, left ventricular (LV) contractile dysfunction and electrocardiographic abnormalities in pressure overload-induced cardiac hypertrophy. The rats were divided into five groups such as sham, aortic stenosis (AS), AS+FLC, AS+O-3-FA and AS+FLC+O-3-FA. Cardiac hypertrophy was produced in rats by abdominal aortic constriction. The rats were treated with FLC (400mg/kg, p.o.), O-3-FA (400mg/kg, p.o.) and FLC+O-3-FA orally per day for four weeks. The LV function, myocardial apoptosis, and oxidative stress were quantified. FLC+O-3-FA treatment significantly reduced hemodynamic changes, improved LV contractile dysfunction, reduced cardiomyocyte apoptosis and cellular oxidative stress. Moreover, it significantly up-regulated the VEGF expression and decreased TNF-alpha level in serum. The histological analysis also revealed that FLC+O-3-FA treatment markedly preserved the cardiac structure and inhibited interstitial fibrosis.

In conclusion, FLC+O-3-FA treatment improved LV dysfunction, inhibited cardiomyocyte apoptosis, improved myocardial angiogenesis, conserved activities of membrane-bound phosphatase enzymes and suppressed inflammation through reduced oxidative stress in an additive manner than FLC alone and O-3-FA alone treatment in pressure overload-induced cardiac hypertrophy.

KEYWORDS:

Antioxidants; Apoptosis; Cardiac hypertrophy; Electrocardiography; Flax lignan concentrate; Omega-3-fatty acid; ROS; TNF-α; VEGF

PMID : 26277701

 

Impact of dietary flaxseed (linum usitatissimum) supplementation on biochemical profile in healthy rats.

Abstract

Flaxseed has been suggested play preventive and therapeutic roles in cardiovascular disease. The aim of this study was to evaluate the influence of flaxseed-supplemented dietary in healthy rats. We used 30 rats divided in three groups (n = 10): Control Group (C) was fed with a casein-based chow (10% protein; 5% fiber; 7% lipid); Flaxseed Group (F) was fed with the casein-based chow supplemented with 25% flaxseed (10% protein; 7% fiber; 11% lipid); Internal Control Group (IC) was fed with the casein-based chow plus soybean oil and fiber (10% protein; 7% fiber; 11% lipid). The blood was obtained by cardiac puncture (after 180 days) and the serum was separated for lipid profile, glucose and uricacid analyses by commercial kit. Although all groups fed the same amount of ration, F group presented low (p < 0.05) body mass than C and IC groups. Total cholesterol and triacylgycerol were similar between all groups. F group presented HDL-C (High-density lipoprotein cholesterol) increase (p < 0.05) in 47% when compared C group. The LDL-C (Low-density lipoprotein cholesterol), glucose and uric acid were reduced (p < 0.05) 22%, 78% 64%, respectively, in F compared to C group.

All results together suggest that the supplementation with 20% o flaxseed might be important to prevent cardiovascular disorders.

PMID: 22470026

 

Mental Health / Cognitive / Neurological

 

Randomized, placebo-controlled trial of flax oil in pediatric bipolar disorder.

Abstract

OBJECTIVES:

This clinical trial evaluated whether supplementation with flax oil, containing the omega-3 fatty acid alpha-linolenic acid (alpha-LNA), safely reduced symptom severity in youth with bipolar disorder.

METHODS:

Children and adolescents aged 6-17 years with symptomatic bipolar I or bipolar II disorder (n = 51), manic, hypomanic, mixed, or depressed, were randomized to either flax oil capsules containing 550 mg alpha-LNA per 1 gram or an olive oil placebo adjunctively or as monotherapy. Doses were titrated to 12 capsules per day as tolerated over 16 weeks. Primary outcomes included changes in the Young Mania Rating Scale, Child Depression Rating Scale-Revised, and Clinical Global Impressions-Bipolar ratings using Kaplan-Meier survival analyses.

RESULTS:

There were no significant differences in primary outcome measures when compared by treatment assignment. However, clinician-rated Global Symptom Severity was negatively correlated with final serum omega-3 fatty acid compositions: %alpha-LNA (r = -0.45, p < 0.007), % eicosapentaenoic acid (EPA) (r = -0.47, p < 0.005); and positively correlated with final arachidonic acid (AA) (r = 0.36, p < 0.05) and docosapentaenoic acid (DPA) n-6 (r = 0.48, p < 0.004). The mean duration of treatment for alpha-LNA was 11.8 weeks versus 8 weeks for placebo; however, the longer treatment duration for alpha-LNA was not significant after controlling for baseline variables. Subjects discontinued the study for continued depressive symptoms.

CONCLUSIONS:

Studies of essential fatty acid supplementation are feasible and well tolerated in the pediatric population. Although flax oil may decrease severity of illness in children and adolescents with bipolar disorder who have meaningful increases in serum EPA percent levels and/or decreased AA and DPA n-6 levels, individual variations in conversion of alpha-LNA to EPA and docosahexaenoic acid as well as dosing burden favor the use of fish oil both for clinical trials and clinical practice. Additionally, future research should focus on adherence and analysis of outcome based on changes in essential fatty acid tissue compositions, as opposed to group randomization alone.

PMID : 20402707

The Role of Nutrients in Protecting Mitochondrial Function and Neurotransmitter Signaling: Implications for the Treatment of Depression, PTSD, and Suicidal Behaviors.

Abstract

Numerous studies have linked severe stress to the development of major depressive disorder(MDD) and suicidal behaviors. Furthermore, recent preclinical studies from our laboratory and others have demonstrated that in rodents, chronic stress and the stress hormone cortisol cause oxidative damage to mitochondrial function and membrane lipids in the brain. Mitochondria play a key role in synaptic neurotransmitter signaling by providing adenosine triphosphate (ATP), mediating lipid and protein synthesis, buffering intracellular calcium, and regulating apoptotic and resilience pathways. Membrane lipids are similarly essential to central nervous system (CNS) function because cholesterol, polyunsaturated fatty acids, and sphingolipids form a lipid raft region, a special lipid region on the membrane that mediates neurotransmitter signaling through G-protein-coupled receptors and ion channels. Low serum cholesterol levels, low antioxidant capacity, and abnormal early morning cortisol levels are biomarkers consistently associated with both depression and suicidal behaviors. In this review, we summarize the manner in which nutrients can protect against oxidative damage to mitochondria and lipids in the neuronal circuits associated with cognitive and affective behaviors. These nutrients include ω3 fatty acids, antioxidants (vitamin C and zinc), members of the vitamin B family (Vitamin B12 and folic acid), and magnesium. Accumulating data have shown that these nutrients can enhance neurocognitive function, and may have therapeutic benefits for depression and suicidal behaviors.

A growing body of studies suggests the intriguing possibility that regular consumption of these nutrients may help prevent the onset of mood disorders and suicidal behaviors in vulnerable individuals, or significantly augment the therapeutic effect of available antidepressants. These findings have important implications for the health of both military and civilian populations.

KEYWORDS:

Vitamin; lipid; oxidative stress; suicide; synaptic plasticity; zinc

PMID : 25365455

 

The effects of omega-3 fatty acids and vitamin E co-supplementation on clinical and metabolic status in patients with Parkinson‘s disease: A randomized, double-blind, placebo-controlled trial.

Depression and altered serum lipids in cynomolgus monkeys consuming a Western diet.

Abstract

Research over the past 15 years has suggested a high comorbidity of depression and coronary heart disease (CHD). However the mechanisms responsible for this relationship are poorly understood. This study was designed to examine the relationships between depressivebehaviors and concentrations of circulating lipids and lipid signaling molecules that may be common to both CHD and depression in a cohort of cynomolgus monkeys (Macaca fascicularis) consuming a ‘Western’ diet, enriched with saturated fat and cholesterol. Socially-housed adult female cynomolgus monkeys (n=36) were fed the Western diet for 27 months and depressive behavior was recorded weekly. Body weight, body mass index and circulating cholesterol profiles were measured in all animals, and fatty acids (FA) and FA-based signaling molecules were measured in the 6 least and 6 most depressed monkeys. Monkeys consuming the Western diet exhibited a broad range of percent time spent in depressive behavior. The percent time spent depressed was positively correlated with total plasma and LDL cholesterol and negatively correlated with HDL cholesterol. Despite being leaner, depressed monkeys had higher concentrations of monounsaturated fats (C16:1 and C17:1), a higher ω6/ω3 polyunsaturated fatty acid (PUFA) ratio and higher concentrations of omega-6 (ω6) PUFAs, particularly C18:2ω6 and C20:3ω6. FA ratios suggest that stearoyl CoA desaturase 1 activity was increased in depressed monkeys. Depressed female cynomolgus monkeys had elevated concentrations of serum lipids and lipid signaling molecules that are typically associated with obesity, insulin resistance and cardiovascular disease, which may account in part for the comorbidity of depression and CHD.

PMID : 21256145

 

Omega-3 Supplementation for Psychotic Mania and Comorbid Anxiety in Children.

Abstract

OBJECTIVES:

Therapeutic benefits of omega-3 fatty acids (Ω3) for mood disorders, psychosis, and anxiety have been reported in the literature. The purpose of the present article is to provide a literature review of Ω3 supplementation for affective disorders and to illustrate the benefits of Ω3 with a case presentation of a young girl with a history of bipolar disorder-type 1 with psychotic features and generalized anxiety disorder.

METHODS:

Reviewed literature includes treatment studies of the impact of Ω3 on child mood disorders supplemented by review of meta-analyses within the adult mood disorders literature. The subject of this case report participated in 11 in-depth diagnostic and functional assessments over 5 years as part of an unrelated study. Three years were presupplementation and 2 years were with supplementation with no other medication changes, thus making a naturalistic multiple-baseline single-subject experiment.

RESULTS:

Augmentation over a 2 year period was notable for clinically significant and sustained improvement in depressive, manic, and psychotic symptoms.

CONCLUSION:

Ω3 supplementation may be a safe, adjunct intervention for treating bipolar disorder in children and adolescents, even in the presence of psychotic and anxious features. The 2 year follow-up in this case offers hope of an accumulating and enduring benefit. Further research into mechanisms of Ω3 action and of combination treatment with other well-known interventions for mood disorders would be beneficial.

PMID : 26288263

Pilot Randomized Controlled Trial of Omega-3 and Individual-Family Psychoeducational Psychotherapy for Children and Adolescents With Depression.

Abstract

The goal of this study is to evaluate feasibility and estimate effect sizes of omega-3 fatty acids (Ω3), individual-family psychoeducational psychotherapy (PEP), their combination, and moderating effects of maternal depression and psychosocial stressors in youth with depression. In a pilot 2 × 2 randomized controlled trial, 72 youth (ages 7-14; 57% Caucasian, 57% male) with major depression, dysthymia, or depression not otherwise specified were randomized to 12 weeks of Ω3, PEP+placebo, Ω3+PEP, or placebo. Ω3 versus placebo was double-masked. Evaluators masked to condition assessed depressive severity at baseline (randomization) and at 2, 4, 6, 9, and 12 weeks using the Children’s Depression Rating Scale-Revised. Side effects were either absent or mild. PEP was administered with 74% fidelity. Remission was 77%, Ω3+PEP; 61%, PEP+placebo; 44%, Ω3; 56%, placebo. Intent-to-treat analyses found small to medium effects of combined treatment (d = .29) and Ω3 monotherapy (d = .42), but negligible effect for PEP+placebo (d < .10), all compared to placebo alone. Relative to placebo, youth with fewer social stressors responded better to Ω3 (p = .04), PEP (p = .028), and their combination (p = .035), and those with maternal depression responded better to PEP (p = .020) than did those without maternal depression. Remission rates were favorable compared to other studies of psychotherapy and comparable to an existing randomized controlled trial of Ω3; results warrant further evaluation in a larger sample. Ω3 was well tolerated. Active treatments show significantly more placebo-controlled depression improvement in the context of maternal depression and fewer stressors, suggesting that they may benefit depression with a more endogenous than environmental origin.

PMID : 27819485

Omega-3 Fatty Acid Plasma Levels Before and After Supplementation: Correlations with Mood and Clinical Outcomes in the Omega-3 and Therapy Studies.

Abstract

OBJECTIVE:

To examine fatty acid profiles, their response to omega-3 fatty acid (Ω3) supplementation, and associations with clinical status and treatment response in youth with mood disorders.

METHODS:

In a placebo-controlled 2X2 design, 7-14 year-olds (N = 95) in parallel pilot trials (depression N = 72; bipolar N = 23) were randomly assigned to 12 weeks of Ω3 supplementation (1.4 g eicosapentaenoic acid [EPA], 0.2 g docosahexaenoic acid [DHA], and 0.27 g other Ω3 per day); psychoeducational psychotherapy (PEP); their combination; or placebo (mainly oleic and linoleic acid) alone. Blood was drawn at baseline (N = 90) and endpoint (n = 65). Fatty acid levels were expressed as percent of total plasma fatty acids. Correlational and moderator/mediator analyses were done with SPSS Statistics 23.

RESULTS:

At baseline: (1) DHA correlated negatively with alpha-linolenic acid (ALA) (r = -0.23, p = 0.029); (2) Arachidonic acid (AA, Ω6) correlated negatively with global functioning (r = -0.24, p = 0.022); (3) Total Ω3 correlated negatively with age (r = -0.22, p = 0.036) and diastolic blood pressure (r = -0.31, p = 0.006). Moderation: Baseline ALA moderated response to Ω3 supplementation: ALA levels above the sample mean (lower DHA) predicted significantly better placebo-controlled response (p = 0.04). Supplementation effects: Compared to placebo, 2 g Ω3 per day increased EPA blood levels sevenfold and DHA levels by half (both p < 0.001). Body weight correlated inversely with increased EPA (r = -0.52, p = 0.004) and DHA (r = -0.54, p = 0.003) and positively with clinical mood response. Mediation: EPA increase baseline-to-endpoint mediated placebo-controlled global function and depression improvement: the greater the EPA increase, the less the placebo-controlled Ω3 improvement.

CONCLUSION:

Ω3 supplementation at 2 g/day increases blood levels substantially, more so in smaller children. A possible U-shaped response curve should be explored.

KEYWORDS:

mediation; moderation; mood disorders; omega-3 fatty acids; plasma levels; supplementation as treatment

PMID : 28157380

Omega-3 supplementation associated with improved parent-rated executive function in youth with mood disorders: secondary analyses of the omega 3 and therapy (OATS) trials.

Abstract

BACKGROUND:

Improvements in executive functioning (EF) may lead to improved quality of life and lessened functional impairment for children with mood disorders. The aim was to assess the impact of omega-3 supplementation (Ω3) and psychoeducational psychotherapy (PEP), each alone and in combination, on EF in youth with mood disorders. We completed secondary analyses of two randomized controlled trials (RCTs) of Ω3 and PEP for children with depression and bipolar disorder.

METHODS:

Ninety-five youths with depression or bipolar disorder not otherwise specified/cyclothymic disorder were randomized in 12-week RCTs. Two capsules (Ω3 or placebo) were given twice daily (1.87 g Ω3 total daily, mostly eicosapentaenoic acid). Families randomized to PEP participated in twice-weekly 50-min sessions. Analyses assess impact of interventions on the Behavior Rating Inventory of Executive Functioning (BRIEF) parent-report Global Executive Composite (GEC) and two subscales, Behavior Regulation (BRI) and Metacognition (MI) Indices. Intent-to-treat repeated measures ANOVAs, using multiple imputation for missing data, included all 95 randomized participants. Trials were registered with www.clinicaltrials.gov, NCT01341925 & NCT01507753.

RESULTS:

Participants receiving Ω3 (aggregating combined and monotherapy) improved significantly more than aggregated placebo on GEC (p = .001, d = .70), BRI (p = .004, d = .49), and MI (p = .04, d = .41). Ω3 alone (d = .49) and combined with PEP (d = .67) each surpassed placebo on GEC. Moderation by attention-deficit/hyperactivity disorder (ADHD) comorbidity was nonsignificant although those with ADHD showed nominally greater gains. PEP monotherapy had negligible effect.

CONCLUSIONS:

Decreased impairment in EF was associated with Ω3 supplementation in youth with mood disorders. Research examining causal associations of Ω3, EF, and mood symptoms is warranted.

© 2017 Association for Child and Adolescent Mental Health.

KEYWORDS:

School children; bipolar disorder; depression; nutrition; psychotherapy

PMID : 29063592

Flaxseed mitigates brain mass loss, improving motor hyperactivity and spatial memory, in a rodent model of neonatal hypoxic-ischemic encephalopathy.

Abstract

Neonatal hypoxic-ischemic (HI) encephalopathy is a major cause of perinatal morbimortality. There is growing evidence that n-3 polyunsaturated fatty acids, especially docosahexaenoic acid (DHA), attenuate brain injury. This study aimed to investigate the possible neuroprotective effect of maternal intake of flaxseed, rich in DHA׳s precursor α-linolenic acid, in the young male offspring subjected to perinatal HI. Wistar rats were divided in six groups, according to maternal diet and offspring treatment at day 7: Control HI (CHI) and Flaxseed HI (FHI); Control Sham and Flaxseed Sham; Control Control and Flaxseed Control. Flaxseed diet increased offspring׳s hippocampal DHA content and lowered depressive behavior. CHI pups presented brain mass loss, motor hyperactivity and poor spatial memory, which were improved in FHI rats.

Maternal flaxseed intake may prevent depressive symptoms in the offspring and promote neuroprotective effects, in the context of perinatal HI, improving brain injury and its cognitive and behavioral impairments.

KEYWORDS:

Depression; Essential fatty acids; Flaxseed; Memory; Neonatal hypoxia-ischemia

PMID : 25865679

Omega-3 for bipolar disorder: meta-analyses of use in mania and bipolar depression.

Abstract

OBJECTIVE:

Studies using augmentation of pharmacotherapies with omega-3 in bipolar disorder have been conducted; however, to date a specific meta-analysis in this area has not been published. Thus, we present the significant findings from meta-analyses of omega-3 in the treatment of bipolar depression and bipolar mania.

DATA SOURCES:

PubMed, CINAHL, Web of Science, and Cochrane Library databases were searched for clinical trials up to September 1, 2010, using the search terms bipolar disorder OR bipolar depression OR bipolar mania OR mania OR hypomania OR cyclothymia with the search terms omega 3 OR essential fatty acids OR polyunsaturated fatty acids OR DHA OR EPA OR fish oil OR flax oil. Clinical trial registries and gray literature (published or unpublished data not readily accessible via main databases) were also searched.

DATA SELECTION:

The analysis included randomized controlled studies 4 weeks or longer, with a sample size > 10, written in English, using omega-3 for diagnosed bipolar depression or mania. No criteria were set for age, gender, or ethnicity.

DATA EXTRACTION:

A random-effects model was used. The model analyzed the standard mean difference between treatment and placebo between baseline and endpoint, combining the effect size (Hedges g) data. Funnel plot and heterogeneity analyses (I²) were also performed.

DATA SYNTHESIS:

The findings of 5 pooled datasets (n = 291) on the outcome of bipolar depression revealed a significant effect in favor of omega-3 (P = .029), with a moderate effect size of 0.34. On the outcome of mania, 5 pooled datasets (n = 291) revealed a nonsignificant effect in favor of omega-3 (P = .099), with an effect size of 0.20. Minor heterogeneity between studies on the outcome of bipolar depression was found (I² = 30%; P = .213), which was not present on the outcome of bipolar mania (I² = 0%; P = .98). Funnel plot symmetry suggested no significant likelihood of publication bias. Meta-regression analysis between sample size and effect size, however, revealed that studies with smaller sample sizes had larger effect sizes (P = .05).

CONCLUSIONS:

The meta-analytic findings provide strong evidence that bipolar depressive symptoms may be improved by adjunctive use of omega-3. The evidence, however, does not support its adjunctive use in attenuating mania.

© Copyright 2012 Physicians Postgraduate Press, Inc.

PMID: 21903025

The antidepressant effect of secoisolariciresinol, a lignan-type phytoestrogen constituent of flaxseed, on ovariectomized mice.

Abstract

Secoisolariciresinol (SECO) is a natural lignan-type phytoestrogen constituent mainly found in flaxseed. It can be metabolized in vivo to mammalian lignans of enterodiol and enterolactone, which have been proven to be effective in relieving menopausal syndrome. Depression is one of the most common symptoms of menopausal syndrome, and is currently treated with estrogen replacement and antidepressant therapy. However, due to the serious side-effects of such agents, there are urgent needs for safer and more tolerable treatments. In this paper, using two classical depression models, the forced swimming test and the tail suspension test, we report the antidepressant effect of SECO on ovariectomized (OVX) mice by intragastric administration for 14 consecutive days at doses of 5, 10 and 20 mg/kg. The results showed that SECO (10 mg/kg) treatment could significantly reduce the duration of immobility of OVX mice in these two models compared with the control group (OVX mice + vehicle), which was similar to the positive control imipramine. In addition, SECO treatment could substantially increase brain monoamine (norepinephrine and dopamine) levels in OVX mice.

The present studies showed that SECO can reverse depressive-like behavior and exhibit monoamine-enhancing effects.

PMID : 22476613

 

Anti-depressive effect of polyphenols and omega-3 fatty acid from pomegranate peel and flax seed in mice exposed to chronic mild stress.

Abstract

AIM:

In this study polyphenols from pomegranate peel, and n-3 fatty acids with polyphenols from flax seed were evaluated for their anti depression properties in mice exposed to chronic mild stress (CMS).

METHODS:

A total of 40 mice initially trained to consume 2% sucrose solution for 3 weeks were then divided into five groups of eight each. The first group was the normal control, the remaining four groups were exposed to CMS but were force fed with either: 10 mL water per kg bodyweight per day; imipramine (a standard antidepressant) 15 mg kg bodyweight; 30 mg per kg bodyweight polyphenol equivalent extract from pomegranate peel; or 30 mg polyphenols per kg bodyweight with omega-3 fatty acids present, for 50 days. At the end, blood and brain were analyzed for various biomarkers of depression.

RESULTS:

The flax seed and imipramine groups had significantly increased sucrose consumption, decreased cortisol (blood), decreased epinephrine and norepinephrine concentration, decreased monoamine oxidase A and B activity, and decreased superoxide dismutase activity. Lipid peroxidation was completely inhibited. In contrast, pomegranate peel extract also completely inhibited lipid peroxidation in the brain, and reduced enzyme activity and hormone concentration but to a lesser extent than flax seed.

CONCLUSION:

Polyphenols from flax seed with omega-3 fatty acids were able to reduce all the CMS effects tested compared to polyphenols from pomegranate peel.

© 2013 The Authors. Psychiatry and Clinical Neurosciences © 2013 Japanese Society of Psychiatry and Neurology.

KEYWORDS:

CMS; flax seed; neurotransmitters; pomegranate peel; sucrose

PMID: 24152226

 

Secoisolariciresinol diglucoside is a blood-brain barrier protective and anti-inflammatory agent: implications for neuroinflammation.

The Neuroprotective Effects of Flaxseed Oil Supplementation on Functional Motor Recovery in a Model of Ischemic Brain Stroke: Upregulation of BDNF and GDNF.

α-Linolenic Acid, A Nutraceutical with Pleiotropic Properties That Targets Endogenous Neuroprotective Pathways to Protect against Organophosphate Nerve Agent-Induced Neuropathology.

 Cancer

Antitumorigenic Properties of Omega-3 Endocannabinoid Epoxides

Abstract

PMID: 29856219

FLAX OIL FROM TRANSGENIC LINUM USITATISSIMUM SELECTIVELY INHIBITS IN VITRO PROLIFERATION OF HUMAN CANCER CELL LINES.

Gebarowski T, Gebczak K, Wiatrak B, Kulma A, Pelc K, Czuj T, Szopa J, Gasiorowski K.

Abstract

Emulsions made of oils from transgenic flaxseeds significantly decreased in vitro proliferation of six tested human cancer cell lines in 48-h cultures, as assessed with the standard sulforhodamine assay. However, the emulsions also increased proliferation rate of normal human dermal fibroblasts and, to a lower extend, of keratinocytes. Both inhibition of in vitro proliferation of human cancer cell lines and stimulation of proliferation of normal dermal fibroblasts and keratinocytes were especially strong with the emulsion type B and with emulsion type M.

Oils from seeds of transgenic flax type B and M should be considered as valuable adjunct to standard cytostatic therapy of human cancers and also could be applied to improve the treatment of skin lesions in wound healing.

PMID: 29624271

Anticancer potentiality of lignan rich fraction of six Flaxseed cultivars.

Ezzat SM^1,2, Shouman SA³, Elkhoely A⁴, Attia YM³, Elsesy MS³, El Senousy AS⁵, Choucry MA⁵, El Gayed SH⁵, El Sayed AA⁵, Sattar EA⁵, El Tanbouly N⁵.

Abstract

The objective of our study is to highlight the therapeutic effect and mechanism of action by which purified Flaxseed hydrolysate (PFH) which is a lignan rich fraction exerts its anticancer activity on a human breast cancer cell line (T47D) and in mice bearing tumor. HPLC analysis of PFH of six flaxseed cultivars had shown that PFH of the cultivar Giza 9 (PFH-G9) contains the highest concentration of SDG (81.64 mg/g). The in vitro cytotoxic potentiality of PFH’s of six flaxseed cultivars was screened against a panel of human cancer cell lines. PFH -G9 showed the most significant cytotoxic activity against ER-receptor positive breast cell lines MCF7 and T47D with IC₅₀ 13.8 and 15.8 µg/ml, respectively. Moreover, PFH-G9 reduced the expression of the metastasis marker, 1-α, metalloproteinases and vascular endothelial growth factor (VEGF), one of the most potent stimulators of angiogenesis, while it increased the caspase-3 dependent apoptosis. Our study also showed that dietary intake of 10% of Giza 9 Flaxseeds (FS), fixed oil (FSO) or Flax meal (FSM) twice daily for 3 weeks in mice-bearing solid Ehrlich ascites carcinoma (EAC) resulted in reducing the tumor volume, the expression of estrogen, insulin growth factor, progesterone, VEGF and MMP-2, but enhanced expression of caspase-3.

PMID: 29323210

 

The Flaxseed-Derived Lignan Phenolic Secoisolariciresinol Diglucoside (SDG) Protects Non-Malignant Lung Cells from Radiation Damage.

Abstract

Plant phenolic compounds are common dietary antioxidants that possess antioxidant and anti-inflammatory properties. Flaxseed (FS) has been reported to be radioprotective in murine models of oxidative lung damage. Flaxseed’s protective properties are attributed to its main biphenolic lignan, secoisolariciresinol diglucoside (SDG). SDG is a free radical scavenger, shown in cell free systems to protect DNA from radiation-induced damage. The objective of this study was to investigate the in vitro radioprotective efficacy of SDG in murine lung cells. Protection against irradiation (IR)-induced DNA double and single strand breaks was assessed by γ-H2AX labeling and alkaline comet assay, respectively. The role of SDG in modulating the levels of cytoprotective enzymes was evaluated by qPCR and confirmed by Western blotting. Additionally, effects of SDG on clonogenic survival of irradiated cells were evaluated. SDG protected cells from IR-induced death and ameliorated DNA damage by reducing mean comet tail length and percentage of γ-H2AX positive cells. Importantly, SDG significantly increased gene and protein levels of antioxidant HO-1, GSTM1 and NQO1.

Our results identify the potent radioprotective properties of the synthetic biphenolic SDG, preventing DNA damage and enhancing the antioxidant capacity of normal lung cells; thus, rendering SDG a potential radioprotector against radiation exposure.

KEYWORDS:

DNA damage; SDG; antioxidant; flaxseed; ionizing radiation; lignan; phenolic; radioprotection

PMID : 26703588

Flax seed oil inhibits metastatic melanoma and reduces lung tumor formation in mice.

Abstract

PURPOSE:

Cancer is one of the leading causes of mortality worldwide. Tumor cells circulating in the blood evidence the migration of tumor from the site of origin to another site leading to the formation of new metastatic lesion and establishment of metastatic tumors. In the present study, cultured metastatic tumor cells were injected into the C57BL/6 mice through tail-vein injection (TVI) and the anti-metastatic properties of flax seed oil (FSO) were evaluated.

METHODS:

Pre-administration of FSO in a dose of 0.3 ml/mice/day was performed for 15 days. On 16th and 21st day, mice were challenged with 2×105 /100 μl murine B10 melanoma (YAC-1 suspended in sterile PBS) cells and continued with FSO administration until the end of the experimental period (40 days) to assess the effect on lung metastasis. At the end of experimental period, mice were sacrificed for plasma and lung tissue samples for biochemical and marker studies. Activities of marker enzymes (AST and ALT), enzymic antioxidants (superoxide dismutase/SOD and catalase/CAT), levels of non/enzymic antioxidants (glutathione), oxidation/stress marker (malondialdehyde/MDA) and cytokines (TNF-alpha, IL-2, IFN-gamma and MMP-9) were assessed.

RESULTS:

Elevated marker enzyme activities in serum and altered enzymic and non-enzymic antioxidants were recovered during FSO treatment. Altered metastatic markers levels favoring the formation of metastatic lesions were observed in the disease group. FSO administration re-altered the levels of these markers in the treatment group contributing to better control of metastasis development.

CONCLUSION:

These results support the protective role of FSO against lung cancer metastasis.

PMID : 26854452

 

Aglycone rich extracts of phytoestrogens cause ROS-mediated DNA damage in breast carcinoma cells.

Abstract

Phytoestrogens are known for their physiological role in lowering risk of osteoporosis, heart disease, breast cancer and menopausal symptoms. They are plant derived potent anti-oxidants, but tend to show pro-oxidant effect at higher concentrations. This study has been undertaken to exploit their pro-oxidant effect in the management of cancer. Cancer cells inherently possess high intracellular ROS levels, however, these levels do not cause harm to the cancer cells because of the anti-oxidant enzyme system. So, there is a need for a treatment strategy which could modulate the ROS levels. Breast cancer cell lines MCF-7 and MDA-MB-231 are treated with various concentrations of soyabean aglycone rich extracts (SARE) and flaxseed aglycone rich extracts (FSARE). The treatment brings about a significant decrease in super oxide dismutase (SOD) and glutathione peroxidase (GPx) activity, thereby leading to accumulation of superoxide ion and peroxide in the cells. The catalase (CAT) activity however, did not show a dose dependent change. The intra-cellular reactive oxygen species (ROS) levels increased and a marked change in mitochondrial membrane potential was detected. Cell cycle arrest was seen at S and G2/M phase in MCF-7 cells and high accumulation of cells in Sub G1 phase was seen in MDA-MB-231 cells. Microscopic evaluation indicated apoptotic morphology and DNA damage.

This study suggests an important role of soyabean and flaxseed aglycones in modulating intracellular ROS in breast carcinoma.

KEYWORDS:

Aglycones; MCF-7; MDA-MB-231; Mitochondrial membrane potential; Phytoestrogens; Reactive oxygen species

PMID : 27876207

 

Secoisolariciresinol diglucoside rich extract of L. usitatissimum prevents diabetic colon cancer through inhibition of CDK4.

Abstract

BACKGROUND:

There is increased risk of colon cancer in both men and women having diabetes. The objective of the study was to evaluate the role of Secoisolariciresinol diglucoside rich extract(SRE) of L.usissatisimum(flaxseed) in colon cancer associated with type 2 diabetes mellitus.

MATERIAL AND METHODS:

Diabetes was induced by administering high fat diet with low dose streptozotocin model. After 6 weeks, diabetes was confirmed and 1,2 dimethylhydrazine(25mg/kg, sc) weekly administration was from 6th to 18th weeks. Rats were treated with the SRE(500mg/kg) orally from 6th to 24th week. After 24 weeks, various biochemical and enzymatic parameters were estimated. Animals were sacrificed and colon tissue was separated and subjected to analysis of histopathological, PCNA studies and mRNA expression of CDK4.

RESULTS:

Disease control rats depicted hyperglycaemia, hyperinsulinaemia, elevated pro-inflammatory cytokines and cancer biomarker levels, and marked presence of proliferating cells. Treatment with SRE controlled hyperglycaemia, hyperinsulinaemia, reduced pro-inflammatory cytokines and cancer biomarker levels, and decreased no. of proliferating cells. We found that disease control rats depicted over expression of CDK4 mRNA levels which were reduced by SRE treatment.

CONCLUSIONS:

SRE of L. usitatissimum exhibited chemopreventive effect in colon cancer associated with type 2 diabetes mellitus which might be mediated through inhibition of CDK4.

Copyright © 2016 Elsevier Masson SAS. All rights reserved.

KEYWORDS:

CDK4; Colon cancer associated with type 2 diabetes mellitus; DMH; L. usitatissimum; Secoisolariciresinol diglucoside

PMID : 27470575

 

Omega-3 polyunsaturated fatty acid inhibits the malignant progression of hepatocarcinoma by inhibiting the Wnt/β-catenin pathway

F.-Z. Chang, Q. Wang, Q. Zhang, L.-L. Chang, W. Li

Department of Gastroenterology, Qingdao Hiser Medical Group, Qingdao, China. Leewei22011@163.com

OBJECTIVE: Omega-3 polyunsaturated fatty acid (ω-3 PUFA) has been found to possess anti-cancer potential in previous studies. However, the underlying mechanism of ω-3 PUFA in protecting hepatocarcinoma has not been fully elucidated. This study aims to explore the function of ω-3 PUFA in the development of hepatocarcinoma and its potential mechanism.

PATIENTS AND METHODS: In this study, human hepatocarcinoma cell line Hep G2 was treated with ω-3 PUFA. Cell counting kit-8 (CCK-8) and cell cloning assay were applied to detect the proliferation of Hep G2 cells. In addition, flow cytometry was performed to analyze the cell cycle and apoptosis rate. At the same time, the effect of ω-3 PUFA on invasion and metastasis of hepatocarcinoma cells were analyzed by transwell assay. Moreover, protein levels of key factors in Wnt/β-catenin pathway were detected by Western blot.

RESULTS: Cell proliferation of Hep G2 cells was decreased after ω-3 PUFA treatment in a time- and dose-dependent manner. CCK-8 assay showed that the IC50 value was 12.8 ± 0.67 μmol/L, 8.8 ± 0.43 μmol/L and 4.6 ± 0.42 μmol/L after ω-3 PUFA treatment for 24 h, 48 h and 72 h, respectively. Besides, ratio of Hep G2 cells blocked at G2/M phase after ω-3 PUFA treatment (5 μmol/L, 10 μmol/L and 20 μmol/L) was increased in a dose-dependent manner (p<0.05). Meanwhile, ω-3 PUFA could increase cell apoptosis (p<0.05) and inhibit cell proliferation. In addition, ω-3 PUFA reduced protein expressions of total, cytoplasmic and nuclear β-catenin in Hep G2 cells, indicating that the Wnt/β-catenin pathway is inhibited. Decreased expression levels of Dvl-2, Dvl-3, GSK-3β (p-ser9), c-myc and survivin, and increased expression levels of GSK-3 (p-tyr216) and Axin-2 were observed in Hep G2 cells treated with ω-3 PUFA, but no significant alteration in total GSK-3β protein level was observed (p>0.05).

CONCLUSIONS: Omega-3 PUFA regulates the malignant progression of hepatocarcinoma by inhibiting proliferation and promoting apoptosis of hepatocarcinoma cells via Wnt/β-catenin signaling pathway.

Sourced = https://www.europeanreview.org/article/15504

Adipokines and Vascular Endothelial Growth Factor in Normal Human Breast Tissue in Vivo – Correlations and Attenuation by Dietary Flaxseed.

Abstract

Exposure to sex steroids increases the risk of breast cancer but the exact mechanisms are yet to be elucidated. Events in the microenvironment are important for carcinogenesis. Diet containing phytoestrogens can affect the breast microenvironment and alter the risk of breast cancer. It has previously been shown that estrogen regulates extracellular levels of leptin, adiponectin, and VEGF in normal breast tissue in vivo. Whether these proteins correlate in breast tissue in vivo or if diet addition of flaxseed, a major source of phytoestrogens in Western diets, alters adipokine levels in breast tissue are unknown. We used microdialysis to sample proteins of normal human breast tissue and abdominal subcutaneous fat in situ in 34 pre-and postmenopausal women. In vitro, co-culture of breast cancer cells and primary human adipocytes was used. In vivo, in normal breast tissue, a significant positive correlation between VEGF and leptin was detected. No correlations were found in fat tissue. Co-culture of adipocytes and breast cancer cells per se increased the secretion of VEGF and leptin and enhanced the effects of estradiol compared to culture of either cell type alone. In vitro, inhibition of VEGF diminished the release of leptin while inhibition of leptin had no influence on VEGF secretion. The levels of leptin decreased and adiponectin increased after a dietary addition of 25 g of flaxseed/day for one menstrual cycle.

We conclude that VEGF and leptin correlate significantly in normal human breast tissue in vivo and that dietary addition of flaxseed affect adipokine levels in the breast.

KEYWORDS:

Adiponectin; Diet; Estrogen; Flaxseed; Leptin; Microdialysis

PMID : 27059487

Flavonoid C-glucosides Derived from Flax Straw Extracts Reduce Human Breast Cancer Cell Growth In vitro and Induce Apoptosis

 

Abstract

Flax straw of flax varieties that are grown for oil production is a by product which represents a considerable biomass source. Therefore, its potential application for human use is of high interest. Our research has revealed that flax straw is rich in flavonoid C-glucosides, including vitexin, orientin, and isoorientin. The objective of this study was to evaluate the cytotoxicity and possible proapoptotic effect of flax straw derived C-glucosides of flavonoids in the human breast adenocarcinoma cell line (MCF-7). The effects of flax straw derived flavonoid C-glucosides on cell proliferation of MCF-7 cells were evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) and sulforhodamine B assays. The expression of apoptosis-related genes was assessed by real-time PCR. Our data revealed that flax C-glucosides as well as pure compounds are cytotoxic toward MCF-7 cells and inhibit their proliferation. Moreover, the induction of apoptosis was correlated with the changes in the mRNA level of pro-apoptotic genes. Increased expression of bax and caspase-7, -8, and -9 and decreased mRNA expression of bcl-2 was observed, whereas the mRNA levels of p53 and mdm2 were not altered.

These results clearly demonstrated that flax straw metabolites effectively induced growth inhibition and apoptosis in human breast adenocarcinoma cells.

Keywords: flax straw, flavonoid C-glucosides, MCF-7, human breast carcinoma cells, apoptosis

 

Enterolactone Suppresses Proliferation, Migration and Metastasis of MDA-MB-231 Breast Cancer Cells Through Inhibition of uPA Induced Plasmin Activation and MMPs-Mediated ECM Remodeling

Abstract

BACKGROUND:

To enhance their own survival, tumor cells can manipulate their microenvironment through remodeling of the extra cellular matrix (ECM). The urokinase-type plasminogen activator (uPA) system catalyzes plasmin production which further mediates activation of matrix metalloproteinases (MMPs) and plays an important role in breast cancer invasion and metastasis through ECM remodeling. This provides a potential target for therapeutic intervention of breast cancer treatment. Enterolactone (EL) is derived from dietary flax lignans in the human body and is known to have anti-breast cancer activity. We here investigated molecular and cellular mechanisms of EL action on the uPA-plasmin- MMPs system.

METHODS:

MTT and trypan blue dye exclusion assays, anchorage-dependent clonogenic assays and wound healing assays were carried out to study effects on cell proliferation and viability, clonogenicity and migration capacity, respectively. Real-time PCR was employed to study gene expression and gelatin zymography was used to assess MMP-2 and MMP-9 activities. All data were statistically analysed and presented as mean ± SEM values.

RESULTS:

All the findings collectively demonstrated anticancer and antimetastatic potential of EL with antiproliferative, antimigratory and anticlonogenic cellular mechanisms. EL was found to exhibit multiple control of plasmin activation by down-regulating uPA expression and also up-regulating its natural inhibitor, PAI-1, at the mRNA level. Further, EL was found to down-regulate expression of MMP-2 and MMP-9 genes, and up-regulate TIMP-1 and TIMP-2; natural inhibitors of MMP-2 and MMP-9, respectively. This may be as a consequence of inhibition of plasmin activation, resulting in robust control over migration and invasion of breast cancer cells during metastasis.

CONCLUSIONS:

EL suppresses proliferation, migration and metastasis of MDA-MB-231 breast cancer cells by inhibiting induced ECM remodeling by the ‘uPA-plasmin-MMPs system’.

KEYWORDS:

Enterolactone; breast cancer; Urokinase; type plasminogen activator; matrix metalloproteinases

PMID : 28545187

Effect of flaxseed supplementation on prostatic carcinoma in transgenic mice.

Flaxseed supplementation (not dietary fat restriction) reduces prostate cancer proliferation rates in men presurgery.

Effects of components present in flaxseed on human colon adenocarcinoma Caco-2 cells: Possible mechanisms of flaxseed on colon cancer development in animals.

Abstract

Previous studies from our laboratory have shown chemopreventive effects of dietary flaxseed on azoxymethane-induced colon tumor development in male Fischer rats and Apc(Min) mice. Tumorigenesis is associated with uncontrolled cell growth and loss of apoptosis. Accordingly, the objective of this investigation was to study the effects of mammalian lignans (enterodiol and enterolactone) and ω-3 polyunsaturated fatty acid α-linolenic acid, principal active components in flaxseed on cell proliferation and apoptosis in human colon adenocarcinoma Caco-2 cells, thus elucidating possible mechanism of action. BrdU incorporation assay was used for cell proliferation and fluorescence-activated cell sorting (FACS) analysis of annexin V/propidium iodide staining was used for determining apoptotic cells. Results showed that enterodiol, enterolactone and α-linolenic acid at different concentrations caused a significant (p < 0.05) increase in apoptotic cells and decrease in cell proliferation. Therefore, dietary flaxseed containing α-linolenic acid and lignans causes a decrease in cell proliferation and an increase in apoptosis resulting in the effective chemoprevention for intestinal and colon tumor development.

PMID: 22491182

Enterolactone alters FAK-Src signaling and suppresses migration and invasion of lung cancer cell lines.

Abstract

BACKGROUND:

Systemic toxicity of chemotherapeutic agents and the challenges associated with targeting metastatic tumors are limiting factors for current lung cancer therapeutic approaches. To address these issues, plant-derived bioactive components have been investigated for their anti-cancer properties because many of these agents are non-toxic to healthy tissues. Enterolactone (EL) is a flaxseed-derived mammalian lignan that has demonstrated anti-migratory properties for various cancers, but EL has not been investigated in the context of lung cancer, and its anticancer mechanisms are ill-defined. We hypothesized that EL could inhibit lung cancer cell motility by affecting the FAK-Src signaling pathway.

METHODS:

Non-toxic concentrations of EL were identified for A549 and H460 human lung cancer cells by conducting 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-Dephenyltetrazolium Bromide (MTT) assays. The anti-migratory and anti-invasive potential of EL for lung cancer cell lines was determined by scratch wound healing and Matrigel® invasion assays. Changes in filamentous actin (F-actin) fiber density and length in EL-treated cells were determined using phalloidin-conjugated rhodamine dye and fluorescent microscopy. Vinculin expression in focal adhesions upon EL treatment was determined by immunocytochemistry. Gene and protein expression levels of FAK-Src signaling molecules in EL-treated lung cancer cells were determined using PCR arrays, qRT-PCR, and western blotting.

RESULTS:

Non-toxic concentrations of EL inhibited lung cancer cell migration and invasion in a concentration- and time-dependent manner. EL treatment reduced the density and number of F-actin fibers in lung cancer cell lines, and reduced the number and size of focal adhesions. EL decreased phosphorylation of FAK and its downstream targets, Src, paxillin, and decreased mRNA expression of cell motility-related genes, RhoA, Rac1, and Cdc42 in lung cancer cells.

CONCLUSIONS:

Our data suggest that EL suppresses lung cancer cell motility and invasion by altering FAK activity and subsequent activation of downstream proteins needed for focal adhesion formation and cytoskeletal rearrangement. Therefore, administration of EL may serve as a safe and complementary approach for inhibiting lung tumor cell motility, invasion, and metastasis.

KEYWORDS:

Cell motility; Enterolactone; F-actin; Flaxseed; Focal adhesion; Lung cancer cells; Rho GTPases

PMID : 28068967

 

Flaxseed Consumption Inhibits Chemically Induced Lung Tumorigenesis and Modulates Expression of Phase II Enzymes and Inflammatory Cytokines in A/J Mice.

Flaxseed and its lignans inhibit estradiol-induced growth, angiogenesis, and secretion of vascular endothelial growth factor in human breast cancer xenografts in vivo.

 

FLAX OIL FROM TRANSGENIC LINUM USITATISSIMUM SELECTIVELY INHIBITS IN VITRO PROLIFERATION OF HUMAN CANCER CELL LINES.

Abstract

Emulsions made of oils from transgenic flaxseeds significantly decreased in vitro proliferation of six tested human cancer cell lines in 48-h cultures, as assessed with the standard sulforhodamine assay. However, the emulsions also increased proliferation rate of normal human dermal fibroblasts and, to a lower extend, of keratinocytes. Both inhibition of in vitro proliferation of human cancer cell lines and stimulation of proliferation of normal dermal fibroblasts and keratinocytes were especially strong with the emulsion type B and with emulsion type M.

Oils from seeds of transgenic flax type B and M should be considered as valuable adjunct to standard cytostatic therapy of human cancers and also could be applied to improve the treatment of skin lesions in wound healing.

PMID : 29624271

 

Whole flaxseed diet alters estrogen metabolism to promote 2-methoxtestradiol-induced apoptosis in hen ovarian cancer.

Abstract

The study reported here demonstrates that a flaxseed-supplemented diet causes ovarian tumors in the laying hen to undergo apoptosis, resulting in a reduction of tumor burden, reducing the frequency and severity of ovarian cancer. We have previously shown in normal ovaries that flaxseed and its components down-regulate ERalpha and alter the expression of enzymes that metabolize estrogen. In this study, we analyzed the effects of the two main components of whole flaxseed, ligan and omega 3 fatty acids on estrogen metabolism and the estrogen receptor in ovarian tumors. ER alpha expression was up-regulated in the ovarian tumors and was not affected by diet. Liver CYP1A1 expression was significantly increased by the whole flaxseed diet with a corresponding increase in 2-methoxyestradiol plasma levels. We also observed increased p38 and ERK 1/2 MAPK activation in the ovary as well as an increase in apoptosis in the tumor epithelium. SMAD 7, a factor involved in the 2-methoxyestradiol-mediated apoptosis pathway was also up-regulated in tumors from the whole flaxseed diet group. 2-methoxyestradiol-induced antitumor effects were further validated by in human ovarian cancer cells.

This study details the effect of flaxseed diet on estrogen metabolism and demonstrates the antiovarian cancer effects of 2-methoxyestradiol.

KEYWORDS:

2-Methoxtestradiol; Apoptosis; Estrogen metabolism; Flaxseed; Ovarian cancer

PMID : 28178600

Flaxseed and its components differentially affect estrogen targets in pre-neoplastic hen ovaries.

 

 General

Production of enterodiol from defatted flaxseeds through biotransformation by human intestinal bacteria.

Mastalgia.

Abstract

Potential protective properties of flax lignan secoisolariciresinol diglucoside

Abstract

Flaxseed and Diabetes

Herbacetin, a flaxseed flavonoid, ameliorates high percent dietary fat induced insulin resistance and lipid accumulation through the regulation of hepatic lipid metabolizing and lipid-regulating enzymes.

Dietary Flaxseed Oil Prevents Western-Type Diet-Induced Nonalcoholic Fatty Liver Disease in Apolipoprotein-E Knockout Mice.

Therapeutic effect of Linum usitatissimum (flaxseed/linseed) fixed oil on acute and chronic arthritic models in albino rats.

Differential effects of dietary flaxseed protein and soy protein on plasma triglyceride and uric acid levels in animal models.

Beneficial effect of flax seeds in streptozotocin (STZ) induced diabetic mice: isolation of active fraction having islet regenerative and glucosidase inhibitory properties.

Flaxseed Protects Against Diabetes-Induced Glucotoxicity by Modulating Pentose Phosphate Pathway and Glutathione-Dependent Enzyme Activities in Rats.

Abstract

This study investigated the effects of flaxseed (Linum usitatissimum L.) intake on general metabolism, pentose phosphate pathway (PPP) and glutathione-dependent enzymes in diabetic rats. Diabetes was induced by streptozotocin injection (40 mg/kg, i.p.) and the enzyme activities were determined spectrophotometrically. Diabetic and control rats were divided in two subgroups, one untreated, and one treated with flaxseed (0.714 g/kg body weight/day; orally) for 12 weeks. Flaxseed ameliorated decreased body weight (p < .05) and increased blood glucose (p < .001), triglyceride (p < .001), ALT (p < .001) and AST (p < .001) in diabetic rats. Diabetes resulted in increased glucose-6-phosphate dehydrogenase (G6PD) (p < .05) and decreased glutathione-S-transferase (GST) (p < .01), but unchanged 6-phosphogluconate dehydrogenase (6PGD) and glutathione reductase (GR) in the brain of rats. These alterations were partially improved by flaxseed in comparison to diabetic untreated group (p < .05). G6PD, 6PGD, GR were elevated (p < .001), while GST unchanged in the lung of diabetic untreated group compared to control. Flaxseed partially prevented the increase in 6PGD (p < .05) and GR (p < .01), but unaffected G6PD in the lung of diabetic rats. G6PD (p < .001), 6PGD (p < .05), GR (p < .001) were augmented, while GST showed a significant (p < .001) depletion in the pancreas of diabetic untreated rats compared to control.

Diabetic alterations observed in pancreatic enzyme activities were significantly prevented by flaxseed. Furthermore, a remarkable decrease in 6PGD (p < .001) and an increase in G6PD (threefold of control) were found in the lens of diabetic untreated group that were completely prevented by flaxseed (p < .001).

Flaxseed has beneficial effects against diabetes-induced glucotoxicity by modulating G6PD, 6PGD, GR and GST activities in tissues.

KEYWORDS:

diabetic rat; flaxseed; glucotoxicity; glutathione-dependent enzymes; pentose phosphate pathway

PMID : 26317558

Flaxseed modulates inflammatory and oxidative stress biomarkers in cystic fibrosis: a pilot study.

Abstract

BACKGROUND:

Cystic fibrosis (CF) leads to advanced lung disease despite aggressive care. Persistent inflammation and oxidative stress contribute to exacerbations and disease progression. Flaxseed (FS), a dietary botanical supplement with high fiber, lignan phenolics, and omega-3 fatty acids has anti-inflammatory and antioxidant properties in murine models of acute and chronic lung injury. This pilot study was designed to determine whether CF patients could tolerate FS, evaluate circulating FS metabolites, and study biomarkers of lung damage, as a prelude to studying clinical outcomes.

METHODS:

10 CF patients and 5 healthy volunteers consumed 40 g of FS daily for 4 weeks with safety and tolerability being assessed. Urine was evaluated for systemic oxidative stress and plasma for FS metabolites (enterolignans) and cytokine levels. Buccal swabs were analyzed for gene expression of Nrf2-regulated antioxidant enzymes including Heme Oxygenase-1 (HO-1) and NAD(P)H Quinone Oxidoreductase 1 (NQO1).

RESULTS:

All subjects completed the study without serious adverse events. Plasma levels of enterolignans were detectable in both healthy controls and CF volunteers. CF patients were stratified based on plasma enterolignan levels after 2 weeks of FS administration into high- (174 to 535 nM ED and 232 to 1841 nM EL) and low- (0 to 32 nM ED and 0 to 40 nM EL) plasma lignan cohorts. The low enterolignan level cohort experienced a statistically significant drop in urinary inflammatory IsoP and plasma TNFα levels, while demonstrating higher average NQO1 mRNA levels in buccal epithelium compared to high-lignan patients.

CONCLUSIONS:

This pilot study demonstrated that FS is tolerated by CF patients. FS metabolites could be detected in the plasma. Future studies will assess appropriate dosing and target populations for FS, while exploring clinical outcomes.

TRIAL REGISTRATION:

ClinicalTrials.gov identifier: NCT02014181 .

PMID : 25963404

Long-chain omega-3 fatty acids and the brain: a review of the independent and shared effects of EPA, DPA and DHA.

Abstract

Omega-3 polyunsaturated fatty acids (PUFAs) exhibit neuroprotective properties and represent a potential treatment for a variety of neurodegenerative and neurological disorders. However, traditionally there has been a lack of discrimination between the different omega-3 PUFAs and effects have been broadly accredited to the series as a whole. Evidence for unique effects of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and more recently docosapentaenoic acid (DPA) is growing. For example, beneficial effects in mood disorders have more consistently been reported in clinical trials using EPA; whereas, with neurodegenerative conditions such as Alzheimer’s disease, the focus has been on DHA. DHA is quantitatively the most important omega-3 PUFA in the brain, and consequently the most studied, whereas the availability of high purity DPA preparations has been extremely limited until recently, limiting research into its effects. However, there is now a growing body of evidence indicating both independent and shared effects of EPA, DPA and DHA. The purpose of this review is to highlight how a detailed understanding of these effects is essential to improving understanding of their therapeutic potential. The review begins with an overview of omega-3 PUFA biochemistry and metabolism, with particular focus on the central nervous system (CNS), where DHA has unique and indispensable roles in neuronal membranes with levels preserved by multiple mechanisms. This is followed by a review of the different enzyme-derived anti-inflammatory mediators produced from EPA, DPA and DHA. Lastly, the relative protective effects of EPA, DPA and DHA in normal brain aging and the most common neurodegenerative disorders are discussed.

With a greater understanding of the individual roles of EPA, DPA and DHA in brain health and repair it is hoped that appropriate dietary recommendations can be established and therapeutic interventions can be more targeted and refined.

KEYWORDS:

Alzheimer’s disease; Parkinson’s disease; aging; docosahexaenoic acid; docosapentaenoic acid; eicosapentaenoic acid; omega-3 fatty acids

PMID : 25954194

Omega-3 polyunsaturated fatty acid blood biomarkers increase linearly in men and women after tightly controlled intakes of 0.25, 0.5, and 1 g/d of EPA + DHA.

Abstract

Blood levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been related to coronary heart disease risk. Understanding the response of EPA + DHA in blood to dietary intake of EPA + DHA would facilitate the use of blood measures as markers of adherence and enable the development of dietary recommendations. The objective of this study is examine the blood response to intakes of EPA + DHA ≤1 g/d with an intervention designed for dietary adherence. It was hypothesized this relationship would be linear and that intakes of EPA + DHA <1 g/d would result in blood levels below those associated with the highest level of protection for cardiovascular events. Background EPA + DHA intake of men and women (n = 20) was determined by food frequency questionnaire and adherence was monitored by weekly fingertip blood sampling for fatty acid determinations. Participants consumed nutraceuticals to achieve intakes of 0.25 g/d and 0.5 g/d EPA + DHA for successive four-week periods. A subgroup (n = 5) had intakes of 1.0 g/d EPA + DHA for an additional 4 weeks. Fatty acid composition of whole blood, erythrocytes, and plasma phospholipids were determined at each time point. Blood levels of EPA and DHA increased linearly in these pools. A comprehensive review of the literature was used to verify the blood-intake relationship. Blood levels of long chain omega-3 polyunsaturated fatty acids reached blood levels associated with the highest levels of primary cardiac arrest reduction and sudden cardiac death risk only with intakes of 1.0 g/d of EPA + DHA. The blood biomarker response to intakes of EPA + DHA ≤1 g/d is linear in a small but highly adherent study sample and this information can assist in determining adherence in clinical studies and help identify dietary intake targets from associations between blood and disease.

KEYWORDS:

Biomarkers; Blood; Docosahexaenoic acid; Dose response; Eicosapentaenoic acid; Humans; Nutrition assessment

PMID : 26500082

Hydroalcoholic extract of flaxseed improves polycystic ovary syndrome in a rat model.

Abstract

OBJECTIVES:

Herbal medicines are an alternative choice for treatment or controlling of polycystic ovary syndrome (PCOS). Effect of hydroalcoholic extract of flaxseed was evaluated on ovarian hormones and histological changes of uterus and ovary in a PCOS-induced rat model.

MATERIALS AND METHODS:

Twenty four rats divided into four groups including negative control, positive control, PCOS and treatment groups. Positive control group received hydroalcoholic extract of flaxseed for 30 days. PCOS was induced by single intramuscular injection of estradiol valerate. Treatment group was treated with flaxseed extract 7 weeks after induction of PCOS for 30 days. Ovaries and uterus were dissected out and their sections were used for histomorphometric study. Levels of estradiol, progesterone, testosterone and dehydroepiandrosterone (DHEA) were measured in the serum.

RESULTS:

In the treatment group, flaxseed extract increased level of progesterone (P<0.05), while decreased testosterone (P<0.05) compared with the PCOS group. Concentrations of estrogen and DHEA did not change significantly in comparison with the PCOS group. Histomorphometric study showed that in the treatment group, the number of preantral follicles, antral follicles and corpus luteum increased compared with the PCOS group (P<0.05), but the number of cystic follicles and diameter of antral follicles decreased (P<0.05), and the number of primary follicle did not alter significantly. In the treatment group, the thickness of granulosa layer increased, but the thickness of theca layer and tunica albuginea decreased compared to the PCOS group (P<0.05).

CONCLUSION:

Hormonal profile and histomorphometric features of ovary that were disturbed by PCOS induction were ameliorated by hydroalcoholic extract of flaxseed.

KEYWORDS:

Flax; Ovary; Polycystic ovary syndrome Rats; Sex hormones; Uterus

PMID : 29942457

The Effect of Flaxseed Supplementation on Hormonal Levels Associated with Polycystic Ovarian Syndrome: A Case Study

Pre-post levels of physiologic measures are provided in Table 1 along with normal reference ranges. A significant decrease in androgen levels was observed, with a 70% decrease in total serum testosterone, an 89% decrease in free serum testosterone, and a 65% decrease in the % free testosterone observed. The patient also reported a decrease in hirsutism at the conclusion of the 4-month period, though no formal measures were taken, In addition, despite a modest amount of weight loss (0.9 kg) the patient’s insulin levels increased 37%; however, remained well within the reference range.

TABLE 1

Manipulation of flaxseed inhibits tumor necrosis factor-alpha and interleukin-6 production in ovarian-induced osteoporosis.

Incorporation of Flaxseed Flour as a Dietary Source for ALA Increases Bone Density and Strength in Post-Partum Female Rats.

An altered tissue distribution of flaxseed lignans and their metabolites in Abcg2 knockout mice.

Abstract

Lignans are dietary polyphenols, which are metabolized by gut microbiota into the phytoestrogenic metabolites enterolignans, mainly enterolactone and enterodiol. Breast Cancer Resistance Protein (BCRP/ABCG2) is an efflux transporter that affects the plasma and milk secretion of several drugs and natural compounds. We hypothesized here that Abcg2 could influence the levels of lignans and their derived metabolites in target tissues. Consequently, we aimed to evaluate the role of Abcg2 in the tissue distribution of these compounds. We used Abcg2^-/- knockout and wild-type male mice fed with a lignan-enriched diet for one week and analysed their plasma, small intestine, colon, liver, kidneys and testicles. High levels of lignans as well as enterolignans and their glucuronide and sulfate conjugates in the small intestine and colon were detected, with higher concentrations of the conjugates in the wild-type compared with Abcg2^-/- mice. Particularly relevant was the detection of 24-fold and 8-fold higher concentrations of enterolactone-sulfate and enterolactone-glucuronide, respectively, in the kidney of Abcg2^-/- compared with wild-type mice.

In conclusion, our study showed that lignans and their derived metabolites were in vivo substrates of Abcg2, which affected their plasma and tissue levels. These results highlight the role of Abcg2 in influencing the health-beneficial properties of dietary lignans.

PMID : 29292449

 

 Protective role of Ashwagandharishta and flax seed oil against maximal electroshock induced seizures in albino rats.

Abstract

Ashwagandharishta, an Ayurvedic classical formulation, is the remedy for Apasmara (epilepsy), Murchha (syncope), Unmada (psychosis), etc. Recent studies in animal models have shown that n-3 PUFAs can raise the threshold of epileptic seizures. The indigenous medicinal plant, called Atasi (Linum usitatissimum Linn.) in Ayurveda, or flax seed, is the best plant source of omega-3 fatty acids. The present study is designed to investigate whether Ashwagandharishta and Atasi taila (flax seed oil) protect against maximal electroshock (MES) seizures in albino rats. Further, a possible protective role of flax seed oil as an adjuvant to Ashwagandharishta in its anticonvulsant activity has also been evaluated in the study. MES seizures were induced for rats and seizure severity was assessed by the duration of hind limb extensor phase. Phenytoin was used as the standard antiepileptic drug for comparison. Both flax seed oil and Ashwagandharishta significantly decreased convulsion phase. Pre-treatment with flax seed oil exhibited significant anticonvulsant activity by decreasing the duration of tonic extensor phase. Contrary to the expectations, pre-treatment with flax seed oil as an adjuvant to Ashwagandharishta failed to decrease the tonic extensor phase; however, it significantly decreased the flexion phase (P < 0.001) and duration of the convulsions (P < 0.05).

Both the drugs exhibited an excellent anti-post-ictal depression effect and complete protection against mortality.

KEYWORDS:

Antiepileptic; Ashwagandharishta; flax seed oil; maximal electroshock seizure; omega-3 fatty acid

PMID: 23049195

Flax lignan concentrate reverses alterations in blood pressure, left ventricular functions, lipid profile and antioxidant status in DOCA-salt induced renal hypertension in rats.

Abstract

CONTEXT:

Earlier we reported cardioprotective, antihyperlipidemic, and in vitro antioxidant activity of flax lignan concentrate (FLC) obtained from the seeds of Linum usitatissimum L. (Linaceae).

OBJECTIVE:

To investigate the effect of FLC in deoxycorticosterone acetate (DOCA)-salt induced experimental renal hypertension in rats.

MATERIALS AND METHODS:

Hypertension was induced in uninephrectomized (UNTZD) male Wistar rats (230-280 g) by injecting DOCA (25 mg/kg, subcutaneously, twice weekly) and supplementing 1% NaCl in drinking water for 5 weeks. The rats were divided in six groups. Captopril (30 mg/kg, p.o.) and FLC (200, 400 and 800 mg/kg, p.o.) were administered daily to the rats of groups III-VI, respectively, for 5 weeks. Various hemodynamic and biochemical parameters were investigated as well as histology of kidney and heart were carried out.

RESULTS:

In this study, the FLC (400 and 800 mg/kg) significantly (p < 0.01, p < 0.001) decreased the systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure. It also significantly (p < 0.01, p < 0.001) decreased elevated end diastolic pressure (EDP), dP/dt max and dP/dt min, organs weights (kidney and heart) and activities of hepatic, renal and cardiac marker enzymes in the serum. Furthermore, FLC (400 and 800 mg/kg) significantly (p < 0.01, p < 0.001) restored altered antioxidant status, serum electrolyte level, lipid profile values, and histological abnormalities. Captopril (30 mg/kg) showed maximum antihypertensive effect but low dose of FLC (200 mg/kg) was not enough to show the antihypertensive activity.

CONCLUSION:

FLC possessed antihypertensive effect via modulation of endogenous enzymes in DOCA-salt induced renal hypertension in rats.

KEYWORDS:

Antihypertensive activity; DOCA; Linum usitatissimum; flaxseed; renal hypertension

PMID : 26795298

Eicosahexanoic Acid (EPA) and Docosahexanoic Acid (DHA) in Muscle Damage and Function.

Abstract

Nutritional supplementation not only helps in improving and maintaining performance in sports and exercise, but also contributes in reducing exercise fatigue and in recovery from exhaustion. Fish oil contains large amounts of omega-3 fatty acids, eicosapentaenoic acid (EPA; 20:5 n-3) and docosahexaenoic acid (DHA; 22:6 n-3). It is widely known that omega-3 fatty acids are effective for improving cardiac function, depression, cognitive function, and blood as well as lowering blood pressure. In the relationship between omega-3 fatty acids and exercise performance, previous studies have been predicted improved endurance performance, antioxidant and anti-inflammatory responses, and effectivity against delayed-onset muscle soreness. However, the optimal dose, duration, and timing remain unclear. This review focuses on the effects of omega-3 fatty acid on muscle damage and function as evaluated by human and animal studies and summarizes its effects on muscle and nerve damage, and muscle mass and strength.

KEYWORDS:

docosahexaenoic acid; eicosapentaenoic acid; muscle damage; muscle hypertrophy; muscle strength; n-3; neuromuscular function; omega3; unsaturated fatty acids

PMID : 29710835

Dietary flaxseed modulates the colonic microenvironment in healthy C57Bl/6 male mice which may alter susceptibility to gut-associated diseases.

Abstract

Understanding how dietary components alter the healthy baseline colonic microenvironment is important in determining their roles in influencing gut health and gut-associated diseases. Dietary flaxseed (FS) has demonstrated anti-colon cancer effects in numerous rodent models, however, exacerbated acute colonic mucosal injury and inflammation in a colitis model. This study investigates whether FS alters critical aspects of gut health in healthy unchallenged mice, which may help explain some of the divergent effects observed following different gut-associated disease challenges. Four-week-old C57Bl/6 male mice were fed an AIN-93G basal diet (BD) or an isocaloric BD+10% ground FS diet for 3 weeks. FS enhanced colon goblet cell density, mucus production, MUC2 mRNA expression, and cecal short chain fatty acid levels, indicative of beneficial intestinal barrier integrity responses. Additionally, FS enhanced colonic regenerating islet-derived protein 3 gamma (RegIIIγ) and reduced MUC1 and resistin-like molecule beta (RELMβ) mRNA expression which may indicate altered responses in regulating microbial defense and injury repair responses. FS diet altered the fecal microbial community structure (16S rRNA gene profiling), including a 20-fold increase in Prevotella spp. and a 30-fold reduction in Akkermansia muciniphila abundance. A 10-fold reduction in A. muciniphila abundance by FS was also demonstrated in the colon tissue-associated microbiota (quantitative PCR). Furthermore, fecal branched chain fatty acids were increased by FS, indicative of increased microbial-derived putrefactive compounds. In conclusion, consumption of a FS-supplemented diet alters the baseline colonic microenvironment of healthy mice which may modify subsequent mucosal microbial defense and injury-repair responses leading to altered susceptibility to different gut-associated diseases.

KEYWORDS:

Akkermansia muciniphila; Flaxseed; Goblet cells; Microbiota; Mucin; Short chain fatty acids

PMID : 26878783

Use of defatted flaxseed meal reduces precancerous colon lesions in C57BL/6 mice.

Abstract

PURPOSE:

To investigate the hemopreventive effect of defatted flaxseed meal in C57BL/6 mice after induction of precancerous colon lesions with 1.2-dimethylhydrazine (DMH).

METHODS:

Thirty-six 12-week-old C57BL/6 mice were divided into three treatment groups(n=12 in each group): (1) diet with 10% defatted flaxseed meal; (2) diet with defatted flaxseed meal and precancerous colon lesions induced by DMH; and (3) precancerous colon lesions induced by DMH, without defatted flaxseed meal. The incidence of aberrant crypt foci (ACF), oxidative processes, expression of tumor suppressor proteins and cyclins, as well as the profile of short-chain fatty acids (SCFA) in animal feces were investigated in the presence and absence of DMH.

RESULTS:

The rats consuming defatted flaxseed meals showed lesions with lower multiplicity and a reduced incidence of lesions. No changes in the expression of tumor suppressor proteins and those involved in cell cycle control were detected.

CONCLUSION:

Defatted flaxseed meal protected the distal colon of mice from precancerous lesions.

PMID : 23896841

Flaxseed extract exhibits mucosal protective effect in acetic acid induced colitis in mice by modulating cytokines, antioxidant and antiinflammatory mechanisms.

Abstract

New treatments for inflammatory bowel disease are of interest due to high rate of remission failure. Natural products have been effective in IBD therapeutics as they have multiple constituents. The aim of the present study was to evaluate the effect of Flaxseed extract (Fs.Cr) on ulcerative colitis and identify the possible mechanisms involved. Colitis was induced by intrarectal administration of 6% AA in BALB/c mice. Colonic mucosal damage was assessed after 24h by calculating disease activity index (DAI), macroscopic and histological damage scores, biochemical measurement of myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and total glutathione activities. Since cytokines are involved in exacerbating inflammatory cascade with emerging role of innate immune cytokines in IBD therapeutics, we hence assessed the effect on the levels of TNF-α, IFN-γ and IL-17, at 6, 12 and 24h by ELISA. Fs.Cr ameliorated the severity of AA colitis as evident by improved DAI, macroscopic damage and the histopathological scores along with restoration of goblet cells. Fs.Cr decreased MDA and MPO activities and enhanced antioxidant activity compared to the AA group. Finally, Fs.Cr in doses (300 and 500mg/kg) decreased TNF-α and IFN-γ levels at all time points with simultaneous increase in IL-17 levels at 24h as compared to the AA group.

These results suggest that Fs.Cr ameliorates the severity of AA colitis by reducing goblet cell depletion, scavenging oxygen-derived free radicals, reduce neutrophil infiltration that may be attributed due to decreasing IFN-γ and TNF-α and increasing IL-17 levels.

KEYWORDS:

Goblet cells; IL-17, IFN-gamma; Innate immune arm; Natural products; Ulcerative colitis

PMID : 27280586

HOLISM STUDY

Professor George Jelinek is Professor and Head of the Neuroepidemiology Unit (NEU) within the Melbourne School of Population and Global Health at The University of Melbourne. The NEU’s charter is to investigate the modifiable lifestyle risk factors that predict the progression of MS with a view to refining a preventive medicine approach to management of the disease.

This large international observational cohort study commenced in 2011 and involved recruitment of an international sample of people with MS through web 2.0 platforms to contribute very detailed, self-reported lifestyle, medication and MS disease outcome data. This is a unique study, being the first study of its type to collect detailed lifestyle data from a very large group of people with MS world-wide and correlate this with outcome, and because it is not funded by industry but by charitable trusts.

PART ONE
The first part of the study collated these data, which are undergoing detailed analysis to determine the association between lifestyle factors and MS disease outcomes as the epidemiological foundation of a secondary and tertiary preventive strategy for managing MS. The database is one of the largest in the world, and is the only database containing a comprehensive suite of modifiable lifestyle risk factors that is independently funded (as opposed to drug company-funded). The study has ethics approval from the Human Research Ethics Committee at St Vincent’s Hospital Melbourne Australia. A number of papers have been published from this database, and further studies are ongoing as follows:

Omega 3 and fish consumption association with MS disease outcomes
This paper reports the strong significant associations of omega 3 intake and frequency of fish consumption with MS disease activity, relapse rate, disability and quality of life for around two and a half thousand people with MS from 57 countries world-wide. It is in this paper that we report the over 60% reduced relapse rate associated with flaxseed oil supplements.

► Jelinek GA, Hadgkiss EJ, Weiland TJ, Pereira N, Marck CH, van der Meer DM. Association of fish consumption and omega 3 supplementation with quality of life, disability and disease activity in an international cohort of people with multiple sclerosis. Int J Neurosci 2013; in press; DOI: 10.3109/00207454.2013.803104 View pdf

Full study : https://overcomingms.org/holism-study/

PLANT-BASED FATTY ACIDS MAY LOWER RISK OF MS

A recent study reported at ECTRIMS (European Committee for Treatment and Research in MS) in Barcelona reports that higher intake of plant-based essential fatty acids, such as alpha linolenic acid in flaxseed oil, may reduce the risk of developing Multiple Sclerosis.

Examining data from the Nurses Health Study on nearly 180,000 nurses in the US, investigators found that individuals who consumed the most foods containing plant-based polyunsaturated fatty acids (PUFAs) had one-third lower MS risk than those individuals consuming the least amount. However, they found no significant association between consuming a diet high in fatty acids from fish and MS risk.

Lead researcher Kjetil Bjørnevik, MD (PhD student), research fellow, University of Bergen, Norway, said: “For the last half a century, there has been a lot of interest in PUFAs (Polyunsaturated Fatty Acids), but it has been mainly focused on fish-derived PUFAs — what we get from consuming fish. Here in our study, we don’t actually see an association between those types of PUFAs and MS risk.” Medical professionals can view the study report at Medscape after signing up at this link.

These findings gave support to the unexpected finding from an earlier publication ​from the OMS Research Team in 2013. In their paper from the HOLISM study Association of fish consumption and omega 3 supplementation with quality of life, disability and disease activity in an international cohort of people with multiple sclerosis, they showed that people with MS consuming flaxseed oil had over 60% lower relapse rate than those not consuming it, but fish oil did not have any significant association. 

It concluded: Those consuming fish more frequently and those taking omega 3 supplements had significantly better quality of life, in all domains, and less disability. For fish consumption, there was a clear dose–response relationship for these associations. There were also trends towards lower relapse rates and reduced disease activity; flaxseed oil supplementation was associated with over 60% lower relapse rate over the previous 12 months. Further dietary studies and randomised controlled trials of omega 3 supplementation for people with MS are required, preferably using flaxseed oil.

While the ECTRIMS report was about risk of developing MS, and the HOLISM report focused on the disease-modifying effect of flaxseed oil intake after developing MS, the studies in combination strongly suggest that the plant-based omega-3s are likely to be the preferred source of omega 3 supplementation for people with MS or those at risk of developing MS, such as their close relatives. Clearly flaxseed oil in particular, the most potent source of plant-based omega 3s, is worthy of ongoing study, and the studies to date reinforce the OMS recommendation to take flaxseed oil rather than fish oil.

Full Paper – International Journal Of Neuroscience

Flaxseed Oil Attenuates Intestinal Damage and Inflammation by Regulating Necroptosis and TLR4/NOD Signaling Pathways Following Lipopolysaccharide Challenge in a Piglet Model.

Dietary α-linolenic acid-rich flaxseed oil prevents against alcoholic hepatic steatosis via ameliorating lipid homeostasis at adipose tissue-liver axis in mice.

Protective effect of alpha-linolenic acid in encephalomalacia in chickens

Inhibitory effect of polyunsaturated fatty acids on apoptosis induced by Streptococcus pneumoniae in alveolar macrophages.

Abstract

Dietary flaxseed oil supplementation mitigates the effect of lead on the enzymes of carbohydrate metabolism, brush border membrane, and oxidative stress in rat kidney tissues.

Potential Contraindication studies :

Dietary flaxseed intake exacerbates acute colonic mucosal injury and inflammation induced by dextran sodium sulfate.

Abstract

Flaxseed (FS), a dietary oilseed, contains a variety of anti-inflammatory bioactives, including fermentable fiber, phenolic compounds (lignans), and the n-3 polyunsaturated fatty acid (PUFA) α-linolenic acid. The objective of this study was to determine the effects of FS and its n-3 PUFA-rich kernel or lignan- and soluble fiber-rich hull on colitis severity in a mouse model of acute colonic inflammation. C57BL/6 male mice were fed a basal diet (negative control) or a basal diet supplemented with 10% FS, 6% kernel, or 4% hull for 3 wk prior to and during colitis induction via 5 days of 2% (wt/vol) dextran sodium sulfate (DSS) in their drinking water (n = 12/group). An increase in anti-inflammatory metabolites (hepatic n-3 PUFAs, serum mammalian lignans, and cecal short-chain fatty acids) was associated with consumption of all FS-based diets, but not with anti-inflammatory effects in DSS-exposed mice. Dietary FS exacerbated DSS-induced acute colitis, as indicated by a heightened disease activity index and an increase in colonic injury and inflammatory biomarkers [histological damage, apoptosis, myeloperoxidase, inflammatory cytokines (IL-6 and IL-1β), and NF-κB signaling-related genes (Nfkb1, Ccl5, Bcl2a1a, Egfr, Relb, Birc3, and Atf1)]. Additionally, the adverse effect of the FS diet was extended systemically, as serum cytokines (IL-6, IFNγ, and IL-1β) and hepatic cholesterol levels were increased. The adverse effects of FS were not associated with alterations in fecal microbial load or systemic bacterial translocation (endotoxemia).

Collectively, this study demonstrates that although consumption of a 10% FS diet enhanced the levels of n-3 PUFAs, short-chain polyunsaturated fatty acids, and lignans in mice, it exacerbated DSS-induced colonic injury and inflammation.

KEYWORDS:

experimental colitis; flaxseed; lignans; n-3 polyunsaturated fatty acids; short-chain fatty acids

PMID: 24763556

• PLEASE NOTE : These studies have hyperlinks to the original location in each title. This is simply the reproduction of, for review purposes only. This does not constitute opinion of the author (chooselife) and certainly not medical advice.