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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 -
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 -
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 -
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 -
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 -
Food & Function Feb 2023Sarcopenia is a syndrome of age-related loss of muscle mass and strength that seriously affects human health, and there are currently no effective drugs to treat the...
Sarcopenia is a syndrome of age-related loss of muscle mass and strength that seriously affects human health, and there are currently no effective drugs to treat the disease. Linolenic acid as a common n-3 polyunsaturated fatty acid (n-3 PUFA) is known to have many beneficial functions. Some studies have found that n-3 PUFA might have the potential to improve sarcopenia. In this study, () was used as a model animal to investigate the effects of linolenic acid on muscles. The results showed that 50 μg mL linolenic acid significantly improved sarcopenia by repairing mitochondrial function by promoting mitophagy and fighting oxidative stress ( < 0.05). This included the increase of the expression of the mitophagy gene and DAF-16/FOXO transcription factors, respectively, by linolenic acid. This study could provide some evidence for the application of n-3 PUFA in improving sarcopenia.
Topics: Animals; Humans; Caenorhabditis elegans; Sarcopenia; alpha-Linolenic Acid; Caenorhabditis elegans Proteins; Mitophagy; Oxidative Stress; Fatty Acids, Omega-3; Forkhead Transcription Factors; Longevity
PubMed: 36651495
DOI: 10.1039/d2fo02974j -
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 -
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 -
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