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Advances in Nutrition (Bethesda, Md.) Oct 2022Given the evidence of the health benefits of plant-based diets and long-chain n-3 (ω-3) fatty acids, there is keen interest in better understanding the role of... (Meta-Analysis)
Meta-Analysis
Given the evidence of the health benefits of plant-based diets and long-chain n-3 (ω-3) fatty acids, there is keen interest in better understanding the role of α-linolenic acid (ALA), a plant-derived n-3 fatty acid, on cardiometabolic diseases and cognition. There is increasing evidence for ALA largely based on its major food sources (i.e., walnuts and flaxseed); however, this lags behind our understanding of long-chain n-3 fatty acids. Meta-analyses of observational studies have shown that increasing dietary ALA is associated with a 10% lower risk of total cardiovascular disease and a 20% reduced risk of fatal coronary heart disease. Three randomized controlled trials (RCTs) [AlphaOmega trial, Prevención con Dieta Mediterránea (PREDIMED) trial, and Lyon Diet Heart Study] all showed benefits of diets high in ALA on cardiovascular-related outcomes, but the AlphaOmega trial, designed to specifically evaluate ALA effects, only showed a trend for benefit. RCTs have shown that dietary ALA reduced total cholesterol, LDL cholesterol, triglycerides, and blood pressure, and epidemiologic studies and some trials also have shown an anti-inflammatory effect of ALA, which collectively account for, in part, the cardiovascular benefits of ALA. A meta-analysis reported a trend toward diabetes risk reduction with both dietary and biomarker ALA. For metabolic syndrome and obesity, the evidence for ALA benefits is inconclusive. The role of ALA in cognition is in the early stages but shows promising evidence of counteracting cognitive impairment. Much has been learned about the health benefits of ALA and with additional research we will be better positioned to make strong evidence-based dietary recommendations for the reduction of many chronic diseases.
Topics: Anti-Inflammatory Agents; Cardiovascular Diseases; Cholesterol, LDL; Cognition; Fatty Acids, Omega-3; Humans; Randomized Controlled Trials as Topic; Triglycerides; Vegetables; alpha-Linolenic Acid
PubMed: 35170723
DOI: 10.1093/advances/nmac016 -
Nutrients May 2019Flaxseed is a rich source of the omega-3 fatty acid, alpha linolenic acid, the lignan secoisolariciresinol diglucoside and fiber. These compounds provide bioactivity of... (Review)
Review
Flaxseed is a rich source of the omega-3 fatty acid, alpha linolenic acid, the lignan secoisolariciresinol diglucoside and fiber. These compounds provide bioactivity of value to the health of animals and humans through their anti-inflammatory action, anti-oxidative capacity and lipid modulating properties. The characteristics of ingesting flaxseed or its bioactive components are discussed in this article. The benefits of administering flaxseed or the individual bioactive components on health and disease are also discussed in this review. Specifically, the current evidence on the benefits or limitations of dietary flaxseed in a variety of cardiovascular diseases, cancer, gastro-intestinal health and brain development and function, as well as hormonal status in menopausal women, are comprehensive topics for discussion.
Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Brain; Butylene Glycols; Cardiovascular Diseases; Diet; Dietary Fiber; Dietary Supplements; Fatty Acids, Omega-3; Female; Flax; Functional Food; Gastrointestinal Diseases; Glucosides; Hormones; Humans; Lignans; Lipid Metabolism; Neoplasms; Seeds; alpha-Linolenic Acid
PubMed: 31130604
DOI: 10.3390/nu11051171 -
BMJ (Clinical Research Ed.) Oct 2021To examine the associations between dietary intake and tissue biomarkers of alpha linolenic acid (ALA) and risk of mortality from all causes, cardiovascular disease... (Meta-Analysis)
Meta-Analysis
Dietary intake and biomarkers of alpha linolenic acid and risk of all cause, cardiovascular, and cancer mortality: systematic review and dose-response meta-analysis of cohort studies.
OBJECTIVE
To examine the associations between dietary intake and tissue biomarkers of alpha linolenic acid (ALA) and risk of mortality from all causes, cardiovascular disease (CVD), and cancer.
DESIGN
Systematic review and meta-analysis of prospective cohort studies.
DATA SOURCES
PubMed, Scopus, ISI Web of Science, and Google Scholar to 30 April 2021.
STUDY SELECTION
Prospective cohort studies that reported the risk estimates for death from all causes, CVD, and cancer.
DATA SYNTHESIS
Summary relative risks and 95% confidence intervals were calculated for the highest versus lowest categories of ALA intake using random effects and fixed effects models. Linear and non-linear dose-response analyses were conducted to assess the dose-response associations between ALA intake and mortality.
RESULTS
41 articles from prospective cohort studies were included in this systematic review and meta-analysis, totalling 1 197 564 participants. During follow-up ranging from two to 32 years, 198 113 deaths from all causes, 62 773 from CVD, and 65 954 from cancer were recorded. High intake of ALA compared with low intake was significantly associated with a lower risk of deaths from all causes (pooled relative risk 0.90, 95% confidence interval 0.83 to 0.97, I=77.8%, 15 studies), CVD (0.92, 0.86 to 0.99, I=48.2%, n=16), and coronary heart disease (CHD) (0.89, 0.81 to 0.97, I=5.6%, n=9), and a slightly higher risk of cancer mortality (1.06, 1.02 to 1.11, I=3.8%, n=10). In the dose-response analysis, a 1 g/day increase in ALA intake (equivalent to one tablespoon of canola oil or 0.5 ounces of walnut) was associated with a 5% lower risk of all cause (0.95, 0.91 to 0.99, I=76.2%, n=12) and CVD mortality (0.95, 0.91 to 0.98, I=30.7%, n=14). The pooled relative risks for the highest compared with lowest tissue levels of ALA indicated a significant inverse association with all cause mortality (0.95, 0.90 to 0.99, I=8.2%, n=26). Also, based on the dose-response analysis, each 1 standard deviation increment in blood concentrations of ALA was associated with a lower risk of CHD mortality (0.92, 0.86 to 0.98, I=37.1%, n=14).
CONCLUSIONS
The findings show that dietary ALA intake is associated with a reduced risk of mortality from all causes, CVD, and CHD, and a slightly higher risk of cancer mortality, whereas higher blood levels of ALA are associated with a reduced risk of all cause and CHD mortality only.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42021229487.
Topics: Cardiovascular Diseases; Eating; Humans; Mortality; Neoplasms; Protective Factors; Risk Assessment; alpha-Linolenic Acid
PubMed: 34645650
DOI: 10.1136/bmj.n2213 -
International Journal of Molecular... Sep 2023Cardiovascular diseases (CVDs) represent the leading cause of global mortality with 1.7 million deaths a year. One of the alternative systems to drug therapy to minimize... (Review)
Review
Cardiovascular diseases (CVDs) represent the leading cause of global mortality with 1.7 million deaths a year. One of the alternative systems to drug therapy to minimize the risk of CVDs is represented by alpha-linolenic acid (ALA), an essential fatty acid of the omega-3 series, known for its cholesterol-lowering effect. The main purpose of this review is to analyze the effects of ALA and investigate the relevant omega-6/omega-3 ratio in order to maintain functionally beneficial effects. Concerning the lipid-lowering preventive effects, ALA may favorably affect the values of LDL-C and triglycerides in both adult and pediatric populations. Furthermore, ALA has shown protective effects against hypertension, contributing to balancing blood pressure through customary diet. According to the 2009 EFSA statement, dietary ALA may contribute to reducing the risk of CVDs, thanks to anti-hypertensive, anti-atherosclerotic and cardioprotective effects.
Topics: Adult; Child; Humans; alpha-Linolenic Acid; Fatty Acids, Omega-3; Hypertension; Antihypertensive Agents; Cardiovascular Diseases
PubMed: 37762621
DOI: 10.3390/ijms241814319 -
International Journal of Molecular... Mar 2023α-linolenic acid (ALA) is an essential C-18 n-3 polyunsaturated fatty acid (PUFA), which can be elongated to longer n-3 PUFAs, such as eicosapentaenoic acid (EPA).... (Review)
Review
α-linolenic acid (ALA) is an essential C-18 n-3 polyunsaturated fatty acid (PUFA), which can be elongated to longer n-3 PUFAs, such as eicosapentaenoic acid (EPA). These long-chain n-3 PUFAs have anti-inflammatory and pro-resolution effects either directly or through their oxylipin metabolites. However, there is evidence that the conversion of ALA to the long-chain PUFAs is limited. On the other hand, there is evidence in humans that supplementation of ALA in the diet is associated with an improved lipid profile, a reduction in the inflammatory biomarker C-reactive protein (CRP) and a reduction in cardiovascular diseases (CVDs) and all-cause mortality. Studies investigating the cellular mechanism for these beneficial effects showed that ALA is metabolized to oxylipins through the Lipoxygenase (LOX), the Cyclooxygenase (COX) and the Cytochrome P450 (CYP450) pathways, leading to hydroperoxy-, epoxy-, mono- and dihydroxylated oxylipins. In several mouse and cell models, it has been shown that ALA and some of its oxylipins, including 9- and 13-hydroxy-octadecatrienoic acids (9-HOTrE and 13-HOTrE), have immunomodulating effects. Taken together, the current literature suggests a beneficial role for diets rich in ALA in human CVDs, however, it is not always clear whether the described effects are attributable to ALA, its oxylipins or other substances present in the supplemented diets.
Topics: Humans; Mice; Animals; Oxylipins; alpha-Linolenic Acid; Cardiovascular Diseases; Eicosapentaenoic Acid; Diet; Fatty Acids, Omega-3
PubMed: 37047085
DOI: 10.3390/ijms24076110 -
International Journal of Molecular... Jun 2021The dietary recommendation encourages reducing saturated fatty acids (SFA) in diet and replacing them with polyunsaturated fatty acids (PUFAs) n-3 (omega-3) and n-6... (Review)
Review
The dietary recommendation encourages reducing saturated fatty acids (SFA) in diet and replacing them with polyunsaturated fatty acids (PUFAs) n-3 (omega-3) and n-6 (omega-6) to decrease the risk of metabolic disturbances. Consequently, excessive n-6 PUFAs content and high n-6/n-3 ratio are found in Western-type diet. The importance of a dietary n-6/n-3 ratio to prevent chronic diseases is linked with anti-inflammatory functions of linolenic acid (ALA, 18:3n-3) and longer-chain n-3 PUFAs. Thus, this review provides an overview of the role of oxylipins derived from n-3 PUFAs and oxylipins formed from n-6 PUFAs on inflammation. Evidence of PUFAs' role in carcinogenesis was also discussed. In vitro studies, animal cancer models and epidemiological studies demonstrate that these two PUFA groups have different effects on the cell growth, proliferation and progression of neoplastic lesions.
Topics: Animals; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Humans; Inflammation; Oxylipins; alpha-Linolenic Acid
PubMed: 34203461
DOI: 10.3390/ijms22136965 -
Cell Adhesion & Migration Dec 2021Microglia, the resident immune cells, were found to be activated to inflammatory phenotype in Alzheimer's disease (AD). The extracellular burden of amyloid-β plaques...
Microglia, the resident immune cells, were found to be activated to inflammatory phenotype in Alzheimer's disease (AD). The extracellular burden of amyloid-β plaques and Tau seed fabricate the activation of microglia. The seeding effect of extracellular Tau species is an emerging aspect to study about Tauopathies in AD. Tau seeds enhance the propagation of disease along with its contribution to microglia-mediated inflammation. The excessive neuroinflammation cumulatively hampers phagocytic function of microglia reducing the clearance of extracellular protein aggregates. Omega-3 fatty acids, especially docosahexaenoic acid and eicosapentaenoic acid, are recognized to induce anti-inflammatory phenotype of microglia. In addition to increased cytokine production, omega-3 fatty acids enhance phagocytic receptors expression in microglia. In this study, we have observed the phagocytosis of extracellular Tau in the presence of α-linolenic acid (ALA). The increased phagocytosis of extracellular Tau monomer and aggregates have been observed upon ALA exposure to microglia cells. After internalization, the degradation status of Tau has been studied with early and late endosomal markers Rab5 and Rab7. Further, the lysosome-mediated degradation of internalized Tau was studied with LAMP-2A, a lysosome marker. The enhanced migratory ability in the presence of ALA could be beneficial for microglia to access the target and clear it. The increased migration of microglia was found to induce the microtubule-organizing center repolarization. The data indicate that the dietary fatty acids ALA could significantly enhance phagocytosis and intracellular degradation of internalized Tau. Our results suggest that microglia could be influenced to reduce extracellular Tau seed with dietary fatty acids.
Topics: Alzheimer Disease; Humans; Microglia; Neuroinflammatory Diseases; Phagocytosis; alpha-Linolenic Acid; tau Proteins
PubMed: 33724164
DOI: 10.1080/19336918.2021.1898727 -
Advances in Nutrition (Bethesda, Md.) Nov 2023Overweight and obesity are highly prevalent worldwide and are associated with cardiovascular disease (CVD) risk factors, including systematic inflammation, dyslipidemia,... (Meta-Analysis)
Meta-Analysis Review
Effect of Alpha-Linolenic Acid Supplementation on Cardiovascular Disease Risk Profile in Individuals with Obesity or Overweight: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Overweight and obesity are highly prevalent worldwide and are associated with cardiovascular disease (CVD) risk factors, including systematic inflammation, dyslipidemia, and hypertension. Alpha-linolenic acid (ALA) is a plant-based essential polyunsaturated fatty acid associated with reduced CVD risks. This systematic review and meta-analysis aimed to investigate the effects of supplementation with ALA compared with the placebo on CVD risk factors in people with obesity or overweight (International Prospective Register of Systematic Reviews Registration No. CRD42023429563). This review included studies with adults using oral supplementation or food or combined interventions containing vegetable sources of ALA. All studies were randomly assigned trials with parallel or crossover designs. The Cochrane Collaboration tool was used for assessing the risk of bias (Version 1). PubMed, Web of Science, Embase, and Cochrane library databases were searched from inception to April 2023. Nineteen eligible randomized controlled trials, including 1183 participants, were included in the meta-analysis. Compared with placebo, dietary ALA supplementation significantly reduced C-reactive protein concentration (standardized mean difference [SMD] = -0.38 mg/L; 95% confidence interval [CI]: -0.72, -0.04), tumor necrosis factor-α concentration (SMD = -0.45 pg/mL; 95% CI: -0.73, -0.17), triglyceride in serum (SMD = -4.41 mg/dL; 95% CI: -5.99, -2.82), and systolic blood pressure (SMD = -0.37 mm Hg; 95% CI: -0.66, -0.08); but led to a significant increase in low-density lipoprotein cholesterol concentrations (SMD = 1.32 mg/dL; 95% CI: 0.05, 2.59). ALA supplementation had no significant effect on interleukin-6, diastolic blood pressure, total cholesterol, or high-density lipoprotein cholesterol (all P ≥ 0.05). Subgroup analysis revealed that ALA supplementation at a dose of ≥3 g/d from flaxseed and flaxseed oil had a more prominent effect on improving CVD risk profiles, particularly where the intervention duration was ≥12 wk and where the baseline CVD profile was poor.
Topics: Adult; Humans; Cardiovascular Diseases; alpha-Linolenic Acid; Overweight; Randomized Controlled Trials as Topic; Cholesterol, HDL; Obesity; Dietary Supplements
PubMed: 37778442
DOI: 10.1016/j.advnut.2023.09.010 -
Molecules (Basel, Switzerland) Apr 2022Fatty acid synthase (FASN) is highly expressed in multiple types of human cancers and is recognized as one of the targets for treating cancer metastasis. α-Linolenic...
Fatty acid synthase (FASN) is highly expressed in multiple types of human cancers and is recognized as one of the targets for treating cancer metastasis. α-Linolenic acid is an omega-3 essential fatty acid and it possesses various biological activities. The present study was designed to reveal the effects of α-linolenic acid on osteosarcoma and to reveal whether the mechanism of α-linolenic acid in anticancer activity may be related to FASN inhibition. The cytotoxicity of α-linolenic acid was assessed in osteosarcoma MG63, 143B, and U2OS cells. Cell viability was detected by the MTT assay. The protein expression level was detected by western blotting. Flow cytometry, Annexin V/propidium iodide dual staining, and Hoechst 33258 staining were performed to assess the apoptotic effects. Wound healing assay was applied to detect the inhibitory effect of α-linolenic acid on osteosarcoma cells migration. The results showed that α-linolenic acid downregulated FASN expression. α-Linolenic acid inhibited osteosarcoma cell proliferation and migration in a dose-dependent manner. In addition, α-linolenic acid regulated endoplasmic reticulum transmembrane receptors and signal protein expression in osteosarcoma cells. The findings of the present study suggested that α-linolenic acid suppresses osteosarcoma cell proliferation and metastasis by inhibiting FASN expression, which provides a basis as a potential target for osteosarcoma treatment.
Topics: Apoptosis; Bone Neoplasms; Cell Line, Tumor; Cell Movement; Cell Proliferation; Fatty Acid Synthases; Humans; Osteosarcoma; alpha-Linolenic Acid
PubMed: 35566090
DOI: 10.3390/molecules27092741 -
Experimental Biology and Medicine... Apr 2023Hyperexcitability is a major mechanism implicated in several neuropsychiatric disorders, such as organophosphate-induced status epilepticus (SE), primary epilepsy,...
Hyperexcitability is a major mechanism implicated in several neuropsychiatric disorders, such as organophosphate-induced status epilepticus (SE), primary epilepsy, stroke, spinal cord injury, traumatic brain injury, schizophrenia, and autism spectrum disorders. Underlying mechanisms are diverse, but a functional impairment and loss of GABAergic inhibitory neurons are common features in many of these disorders. While novel therapies abound to correct for the loss of GABAergic inhibitory neurons, it has been difficult at best to improve the activities of daily living for the majority of patients. Alpha-linolenic acid (ALA) is an essential omega-3 polyunsaturated fatty acid found in plants. ALA exerts pleiotropic effects in the brain that attenuate injury in chronic and acute brain disease models. However, the effect of ALA on GABAergic neurotransmission in hyperexcitable brain regions involved in neuropsychiatric disorders, such as the basolateral amygdala (BLA) and CA1 subfield of the hippocampus, is unknown. Administration of a single dose of ALA (1500 nmol/kg) subcutaneously increased the charge transfer of inhibitory postsynaptic potential currents mediated by GABA receptors in pyramidal neurons by 52% in the BLA and by 92% in the CA1 compared to vehicle animals a day later. Similar results were obtained in pyramidal neurons from the BLA and CA1 when ALA was bath-applied in slices from naïve animals. Importantly, pretreatment with the high-affinity, selective TrkB inhibitor, k252, completely abolished the ALA-induced increase in GABAergic neurotransmission in the BLA and CA1, suggesting a brain-derived neurotrophic factor (BDNF)-mediated mechanism. Addition of mature BDNF (20 ng/mL) significantly increased GABA receptor inhibitory activity in the BLA and CA1 pyramidal neurons similar to the results obtained with ALA. ALA may be an effective treatment for neuropsychiatric disorders where hyperexcitability is a major feature.
Topics: Rats; Humans; Animals; Basolateral Nuclear Complex; alpha-Linolenic Acid; Brain-Derived Neurotrophic Factor; Rats, Sprague-Dawley; Activities of Daily Living; Synaptic Transmission; Receptors, GABA-A
PubMed: 37208920
DOI: 10.1177/15353702231165010