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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 -
Food and Chemical Toxicology : An... Aug 2014α-Linolenic acid (ALA), a carboxylic acid with 18 carbons and three cis double bonds, is an essential fatty acid needed for human health and can be acquired via regular... (Review)
Review
α-Linolenic acid (ALA), a carboxylic acid with 18 carbons and three cis double bonds, is an essential fatty acid needed for human health and can be acquired via regular dietary intake of foods that contain ALA or dietary supplementation of foods high in ALA, for example flaxseed. ALA has been reported to have cardiovascular-protective, anti-cancer, neuro-protective, anti-osteoporotic, anti-inflammatory, and antioxidative effects. ALA is the precursor of longer chain omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), but its beneficial effects on risk factors for cardiovascular diseases are still inconclusive. The recommended intake of ALA for cardiovascular health is reported to be 1.1-2.2g/day. Although there are limited toxicological data for ALA, no serious adverse effects have been reported. The evidence on an increased prostate cancer risk in association with dietary ALA is not conclusive. Based on the limited data currently available, it may be concluded that ALA may be beneficial as a nutraceutical/pharmaceutical candidate and is safe for use as a food ingredient.
Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Antioxidants; Cardiovascular Diseases; Cardiovascular System; Dietary Supplements; Disease Models, Animal; Docosahexaenoic Acids; Dose-Response Relationship, Drug; Eicosapentaenoic Acid; Female; Humans; Male; Neuroprotective Agents; Prostatic Neoplasms; Risk Factors; Toxicity Tests; alpha-Linolenic Acid
PubMed: 24859185
DOI: 10.1016/j.fct.2014.05.009 -
International Journal of Biological... Jan 2021Alzheimer's disease is characterized by important patho-proteins, which being composed of Amyloid-β plaques and intracellular neurofibrillary tangles of Tau....
Alzheimer's disease is characterized by important patho-proteins, which being composed of Amyloid-β plaques and intracellular neurofibrillary tangles of Tau. Intrinsically disordered protein tau has several interacting partners, which are necessary for its normal functioning. Tau has been shown to interact with various proteins, nucleic acid, and lipids. α-Linolenic acid (ALA) a plant-based omega-3 fatty acid has been studied for its role as neuroprotective and beneficial fatty acid in the brain. In this study, we are focusing on the ability of ALA to induce spontaneous assembly in tau protein. ALA inhibited the Tau aggregation as indicated by reduced ThS fluorescence kinetics, which indicates no aggregation of Tau. Similarly, SDS-PAGE analysis supported that ALA exposure inhibited the aggregation as no higher-order tau species were observed. Along with its ability to impede the aggregation of Tau, ALA also maintains a native random coiled structure, which was estimated by CD spectroscopy. Finally, TEM analysis showed that the formation of Tau fibrils was found to be discouraged by ALA. Hence, conclusion of the study suggested that ALA profoundly inhibited aggregation of Tau and maintained it's the random-coil structure.
Topics: Humans; Protein Conformation; Protein Multimerization; Protein Unfolding; alpha-Linolenic Acid; tau Proteins
PubMed: 33130263
DOI: 10.1016/j.ijbiomac.2020.10.226 -
Current Opinion in Clinical Nutrition... Mar 2004This review critically evaluates current knowledge of alpha-linolenic acid metabolism in adult humans based on the findings of studies using stable isotope tracers and... (Review)
Review
PURPOSE OF REVIEW
This review critically evaluates current knowledge of alpha-linolenic acid metabolism in adult humans based on the findings of studies using stable isotope tracers and on increased dietary alpha-linolenic acid intake. The relative roles of alpha-linolenic acid and of longer-chain polyunsaturated fatty acids in cell structure and function are discussed together with an overview of the major metabolic fates of alpha-linolenic acid. The extent of partitioning towards beta-oxidation and carbon recycling in humans is described. The use and limitations of stable isotope tracers to estimate alpha-linolenic acid desaturation and elongation are discussed. A consensus view of the extent of alpha-linolenic acid conversion to longer-chain fatty acids in humans is presented. The extent to which increasing dietary alpha-linolenic acid intake alters the concentrations of longer-chain n-3 fatty acids is described. The biological and nutritional implications of these findings are discussed.
RECENT FINDINGS
Conversion of alpha-linolenic acid to eicosapentaenoic acid is limited in men and further transformation to docosahexaenoic acid is very low. A lower proportion of alpha-linolenic acid is used as a substrate for beta-oxidation in women compared with men, while the fractional conversion to longer-chain fatty acids is greater, possibly due to the regulatory effects of oestrogen.
SUMMARY
Overall, alpha-linolenic acid appears to be a limited source of longer-chain n-3 fatty acids in man and so adequate intakes of preformed n-3 polyunsaturated fatty acids, in particular docosahexaenoic acid, may be important for maintaining optimal tissue function. Capacity to upregulate alpha-linolenic acid transformation in women may be important for meeting the demands of the fetus and neonate for docosahexaenoic acid.
Topics: Carbon Isotopes; Eicosapentaenoic Acid; Energy Metabolism; Fatty Acids, Unsaturated; Female; Humans; Male; Nutritional Requirements; Oxidation-Reduction; Sex Characteristics; alpha-Linolenic Acid
PubMed: 15075703
DOI: 10.1097/00075197-200403000-00006 -
Nutrition, Metabolism, and... Jun 2004To summarize our present knowledge about vegetable omega-3 fatty acids. (Comparative Study)
Comparative Study Review
AIM
To summarize our present knowledge about vegetable omega-3 fatty acids.
DATA SYNTHESIS
Alpha-linolenic acid (ALA) is one of the two essential fatty acids in humans. Epidemiological studies and dietary trials strongly suggest that this fatty acid is important in relation with the pathogenesis (and prevention) of coronary heart disease. Like other n-3 fatty acids from marine origin, it may prevent cardiac arrhythmias and sudden cardiac death. The optimal dietary intake of alpha-linolenic acid seems to be about 2 g per day or 0.6 to 1% of total energy intake. Obtaining an optimal ratio of the two essential fatty acids, linoleic and alpha-linolenic acids--ie a ratio of less than 4 to 1 in the diet--is a major issue. The main sources of alpha-linolenic acid for the European population should be canola oil (and canola-oil based margarine if available), nuts (English walnut), ground linseeds and green leafy vegetables such as purslane.
CONCLUSIONS
Epidemiological studies and dietary trials in humans suggest that alpha-linolenic acid is a major cardio-protective nutrient.
Topics: Biomarkers; Cardiovascular Diseases; Coronary Artery Disease; Dietary Supplements; Female; Humans; Male; Prognosis; Sensitivity and Specificity; alpha-Linolenic Acid
PubMed: 15330276
DOI: 10.1016/s0939-4753(04)80037-1 -
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 -
European Review For Medical and... Nov 2023Methotrexate (MTX) is a folic acid antagonist used in chronic inflammatory diseases and various cancer treatments. Although the main mechanism of the toxic effect of MTX...
OBJECTIVE
Methotrexate (MTX) is a folic acid antagonist used in chronic inflammatory diseases and various cancer treatments. Although the main mechanism of the toxic effect of MTX is not known, it is stated that it causes oxidative stress and inflammation. Alpha-linolenic acid (ALA) protects against oxidative stress, apoptosis, and inflammation. For this reason, we aimed to find out the useful effect of ALA on MTX-induced nephrotoxicity MATERIALS AND METHODS: The mice were divided into 4 groups randomly. The control group was treated with physiological saline solution; the ALA group was treated with ALA (200 mg/kg) by gavage; MTX-treated group received 20 mg/kg i.p. (intraperitoneal) MTX; and MTX+ALA treated group received 20 mg/kg i.p. MTX and ALA 200 mg/kg by gavage. All of the drugs were performed once a day for 9 days.
RESULTS
Alpha-linolenic acid significantly decreased oxidative stress parameters and MTX-induced inflammatory and apoptotic mediators. Furthermore, histopathological examination showed that MTX induced significant edematous damage, and ALA treatment attenuated this damage in renal tissue.
CONCLUSIONS
Our results revealed that ALA may be helpful against MTX-induced nephrotoxicity in mice via its antioxidant and anti-inflammatory properties.
Topics: Mice; Animals; Methotrexate; alpha-Linolenic Acid; Antioxidants; Oxidative Stress; Inflammation; Kidney
PubMed: 38039041
DOI: 10.26355/eurrev_202311_34479 -
Life Sciences Jan 2024Metabolic syndrome (MetS), which is characterized by insulin resistance, high blood glucose, obesity, and dyslipidemia, is known to increase the risk of dementia... (Review)
Review
Metabolic syndrome (MetS), which is characterized by insulin resistance, high blood glucose, obesity, and dyslipidemia, is known to increase the risk of dementia accompanied by memory loss and depression. The direct pathways and specific mechanisms in the central nervous system (CNS) for addressing fatty acid imbalances in MetS have not yet been fully elucidated. Among polyunsaturated acids, linoleic acid (LA, n6-PUFA) and α-linolenic acid (ALA, n3-PUFA), which are two essential fatty acids that should be provided by food sources (e.g., vegetable oils and seeds), have been reported to regulate various cellular mechanisms including apoptosis, inflammatory responses, mitochondrial biogenesis, and insulin signaling. Furthermore, inadequate intake of LA and ALA is reported to be involved in neuropathology and neuropsychiatric diseases as well as imbalanced metabolic conditions. Herein, we review the roles of LA and ALA on metabolic-related dementia focusing on insulin resistance, dyslipidemia, synaptic plasticity, cognitive function, and neuropsychiatric issues. This review suggests that LA and ALA are important fatty acids for concurrent treatment of both MetS and neurological problems.
Topics: Humans; Linoleic Acid; alpha-Linolenic Acid; Insulin Resistance; Fatty Acids; Cognitive Dysfunction; Dyslipidemias; Dementia
PubMed: 38123015
DOI: 10.1016/j.lfs.2023.122356 -
Progress in Lipid Research Jul 2015Docosahexaenoic acid (DHA) is important for brain function, and can be obtained directly from the diet or synthesized in the body from α-linolenic acid (ALA). Debate... (Review)
Review
Docosahexaenoic acid (DHA) is important for brain function, and can be obtained directly from the diet or synthesized in the body from α-linolenic acid (ALA). Debate exists as to whether DHA synthesized from ALA can provide sufficient DHA for the adult brain, as measures of DHA synthesis from ingested ALA are typically <1% of the oral ALA dose. However, the primary fate of orally administered ALA is β-oxidation and long-term storage in adipose tissue, suggesting that DHA synthesis measures involving oral ALA tracer ingestion may underestimate total DHA synthesis. There is also evidence that DHA synthesized from ALA can meet brain DHA requirements, as animals fed ALA-only diets have brain DHA concentrations similar to DHA-fed animals, and the brain DHA requirement is estimated to be only 2.4-3.8 mg/day in humans. This review summarizes evidence that DHA synthesis from ALA can provide sufficient DHA for the adult brain by examining work in humans and animals involving estimates of DHA synthesis and brain DHA requirements. Also, an update on methods to measure DHA synthesis in humans is presented highlighting a novel approach involving steady-state infusion of stable isotope-labeled ALA that bypasses several limitations of oral tracer ingestion. It is shown that this method produces estimates of DHA synthesis that are at least 3-fold higher than brain uptake rates in rats.
Topics: Animals; Biosynthetic Pathways; Brain; Diet; Docosahexaenoic Acids; Humans; alpha-Linolenic Acid
PubMed: 25920364
DOI: 10.1016/j.plipres.2015.04.002 -
Brazilian Journal of Biology = Revista... 2021The objective of the current study was to investigate the synergistic impact of α-Tocopherol and α-Linolenic acid (100 µM) on IVM and IVC of Nili Ravi buffalo...
The objective of the current study was to investigate the synergistic impact of α-Tocopherol and α-Linolenic acid (100 µM) on IVM and IVC of Nili Ravi buffalo oocytes. Oocytes were obtained from the ovaries of slaughtered buffaloes within two hours after slaughter and brought to laboratory. Buffalo cumulus oocyte complexes were placed randomly in the five experimental groups included; GROUP 1: Maturation media (MM) + 100 µM ALA (control), GROUP 2: MM + 100 µM ALA + 50μM α-Tocopherol, GROUP 3: MM + 100 µM ALA + 100μM α-Tocopherol, GROUP 4: MM + 100 µM ALA + 200 μM α-Tocopherol and GROUP 5: MM + 100 µM ALA + 300 μM α-Tocopherol under an atmosphere of 5% CO2 in air at 38.5 °C for 22-24 h. Cumulus expansion and nuclear maturation status was determined (Experiment 1). In experiment 2, oocytes were matured as in experiment 1. The matured oocytes were then fertilized in Tyrode's Albumin Lactate Pyruvate (TALP) medium for about 20 h and cultured in synthetic oviductal fluid (SOF) medium to determine effect of α-Linolenic acid (100 µM) and α-Tocopherol in IVM medium on IVC of presumptive zygotes. To study the effect of α-Linolenic acid (100 µM) in IVM media and increasing concentration of α-tocopherol in the culture media on early embryo development (Experiment 3), the presumptive zygotes were randomly distributed into the five experimental groups with increasing concentration of α-tocopherol in culture media. Higher percentage of MII stage oocytes in experiment 1(65.2±2.0), embryos at morula stage in experiment 2 (30.4±1.5) and experiment 3 (22.2±2.0) were obtained. However, overall results for cumulus cell expansion, maturation of oocyte to MII stage and subsequent embryo development among treatments remain statistically similar (P > 0.05). Supplementation of α-tocopherol in maturation media having α-Linolenic acid and/or in embryo culture media did not further enhance in vitro maturation of oocyte or embryo production.
Topics: Animals; Buffaloes; Culture Media; Embryonic Development; Oocytes; alpha-Linolenic Acid; alpha-Tocopherol
PubMed: 34932678
DOI: 10.1590/1519-6984.253514