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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 -
Acta Dermato-venereologica Sep 2014This study was undertaken to evaluate the clinical efficacy, safety, and histological changes induced by dietary omega-3 fatty acid and γ-linoleic acid in acne... (Randomized Controlled Trial)
Randomized Controlled Trial
This study was undertaken to evaluate the clinical efficacy, safety, and histological changes induced by dietary omega-3 fatty acid and γ-linoleic acid in acne vulgaris. A 10-week, randomised, controlled parallel dietary intervention study was performed in 45 participants with mild to moderate acne, which were allocated to either an omega-3 fatty acid group (2,000 mg of eicosapentaenoic acid and docosahexaenoic acid), a γ-linoleic acid group (borage oil containing 400 mg γ-linoleic acid), or a control group. After 10 weeks of omega-3 fatty acid or γ-linoleic acid supplementation, inflammatory and non-inflammatory acne lesions decreased significantly. Patient subjective assessment of improvement showed a similar result. Heamatoxylin & eosin staining of acne lesions demonstrated reductions in inflammation and immunohistochemical staining intensity for interleukin-8. No severe adverse effect was reported. This study shows for the first time that omega-3 fatty acid and γ-linoleic acid could be used as adjuvant treatments for acne patients.
Topics: Acne Vulgaris; Adolescent; Adult; Dietary Supplements; Docosahexaenoic Acids; Double-Blind Method; Eicosapentaenoic Acid; Female; Humans; Interleukin-8; Male; Prospective Studies; Young Adult; alpha-Linolenic Acid
PubMed: 24553997
DOI: 10.2340/00015555-1802 -
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 -
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 -
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 -
Annals of Nutrition & Metabolism 2016Docosahexaenoic acid (DHA) is a long-chain, highly unsaturated omega-3 (n-3) fatty acid. It has a structure that gives it unique physical and functional properties. DHA...
Docosahexaenoic acid (DHA) is a long-chain, highly unsaturated omega-3 (n-3) fatty acid. It has a structure that gives it unique physical and functional properties. DHA is metabolically related to other n-3 fatty acids: it can be synthesised from the plant essential fatty acid α-linolenic acid (ALA). However, this pathway does not appear to be very efficient in many individuals, although the conversion of ALA to DHA is much better in young women than in young men. Furthermore, young infants may be more efficient converters of ALA to DHA than many adults, although the conversion rate is variable among infants. Many factors have been identified that affect the rate of conversion. The implication of poor conversion is that preformed DHA needs to be consumed. DHA is found in fairly high amounts in seafood, especially fatty fish, and in various forms of n-3 supplements. The amount of DHA in seafood and in supplements varies. Breast milk contains DHA. DHA is found esterified into complex lipids within the bloodstream, in adipose stores and in cell membranes. Its concentration in different compartments varies greatly. The brain and eye have high DHA contents compared to other organs. DHA is especially concentrated in the grey matter of the brain and in the rod outer segments of the retina. In the brain DHA is involved in neuronal signalling, while in the eye it is involved in the quality of vision. DHA is accumulated in the brain and eye late in pregnancy and in early infancy. A lower DHA content is linked to poorer cognitive development and visual function. DHA affects cell and tissue physiology and function through numerous mechanisms, including alterations in membrane structure and function, in membrane protein function, in cellular signalling and in lipid mediator production.
Topics: Adult; Age Factors; Brain; Dietary Supplements; Docosahexaenoic Acids; Female; Humans; Infant; Infant Nutritional Physiological Phenomena; Infant, Newborn; Male; Milk, Human; Seafood; Sex Factors; alpha-Linolenic Acid
PubMed: 27842299
DOI: 10.1159/000448262 -
Nutrients Dec 2022Docosahexaenoic acid (DHA) is a major constituent of neural and visual membranes and is required for optimal neural and visual function. DHA is derived from food or by... (Review)
Review
Docosahexaenoic acid (DHA) is a major constituent of neural and visual membranes and is required for optimal neural and visual function. DHA is derived from food or by endogenous synthesis from α-linolenic acid (ALA), an essential fatty acid. Low blood levels of DHA in some westernised populations have led to speculations that child development disorders and various neurological conditions are associated with sub-optimal neural DHA levels, a proposition which has been supported by the supplement industry. This review searched for evidence of deficiency of DHA in human populations, based on elevated levels of the biochemical marker of -3 deficiency, docosapentaenoic acid (22:5-6). Three scenarios/situations were identified for the insufficient supply of DHA, namely in the brain of new-born infants fed with high-linoleic acid (LA), low-ALA formulas, in cord blood of women at birth who were vegetarians and in the milk of women from North Sudan. Twenty post-mortem brain studies from the developed world from adults with various neurological disorders revealed no evidence of raised levels of 22:5-6, even in the samples with reduced DHA levels compared with control subjects. Human populations most likely at risk of -3 deficiency are new-born and weanling infants, children and adolescents in areas of dryland agriculture, in famines, or are refugees, however, these populations have rarely been studied. This is an important topic for future research.
Topics: Infant, Newborn; Infant; Pregnancy; Adult; Child; Humans; Female; Adolescent; Animals; Docosahexaenoic Acids; Fatty Acids, Essential; Brain; Milk; Parturition; alpha-Linolenic Acid
PubMed: 36615819
DOI: 10.3390/nu15010161 -
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 Nanomedicine 2021Small molecule modified antitumor drug conjugate nanoparticles have the advantages of high drug loading, simple synthesis and preparation, and better biocompatibility....
PURPOSE
Small molecule modified antitumor drug conjugate nanoparticles have the advantages of high drug loading, simple synthesis and preparation, and better biocompatibility. Due to the large demand for exogenous α-linolenic acid (ALA) by tumor cells, we synthesized α-linolenic acid-paclitaxel conjugate (ALA-PTX) and prepared α-linolenic acid-paclitaxel conjugate nanoparticles (ALA-PTX NPs), in order to obtain better tumor cellular uptake and antitumor activity in vitro and in vivo.
METHODS
We synthesized and characterized ALA-PTX, and then prepared and characterized ALA-PTX NPs. The cellular uptake, uptake pathways, intracellular behavior, in vitro and in vivo antitumor activity of ALA-PTX NPs were evaluated.
RESULTS
The size of ALA-PTX NPs was approximately 110.7±1.7 nm. The drug loading was approximately 90% (w/w) with CrEL-free and organic solvent-free characteristics. The cellular uptake of ALA-PTX NPs was significantly higher than that of PTX injection by MCF-7, MCF-7/ADR and HepG2 cells. In these three cell lines, the cellular uptake of ALA-PTX NPs at 6h was approximately 1.5-2.6 times higher than that of PTX injection. ALA-PTX NPs were ingested through clathrin-mediated endocytosis, then transferred to lysosomes, and could dissolve in cells to play an antitumor activity. The in vitro and in vivo antitumor activity of ALA-PTX NPs was confirmed in MCF-7/ADR and HepG2 cell models and tumor-bearing nude mouse models.
CONCLUSION
ALA-PTX NPs developed in our study could provide a new method for the preparation of nano-delivery systems suitable for antitumor therapy that could increase tumor cellular uptake and enhance antitumor activity.
Topics: Animals; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Endocytosis; Mice; Nanoparticles; Paclitaxel; alpha-Linolenic Acid
PubMed: 34737564
DOI: 10.2147/IJN.S331578