-
Nutrients Jan 2020Supplementation with -3 long-chain (LC) polyunsaturated fatty acids (PUFA) is known to promote thermogenesis via the activation of brown adipose tissue (BAT)....
Supplementation with -3 long-chain (LC) polyunsaturated fatty acids (PUFA) is known to promote thermogenesis via the activation of brown adipose tissue (BAT). Agricultural products that are biofortified with -linolenic acid (ALA), the precursor of -3 LC PUFA, have been launched to the market, but their impact on BAT function is unknown. This study aimed to evaluate the effects of ALA-biofortified butter on lipid metabolism and thermogenic functions in the BAT. C57BL/6 mice were fed a high-fat diet containing ALA-biofortified butter (n3Bu, 45% calorie from fat) for ten weeks in comparison with the isocaloric high-fat diets prepared from conventional butter or margarine. The intake of n3Bu significantly reduced the whitening of BAT and increased the thermogenesis in response to acute-cold treatment. Also, n3Bu supplementation is linked with the remodeling of BAT by promoting bioconversion into -3 LC PUFA, FA elongation and desaturation, and mitochondrial biogenesis. Taken together, our results support that ALA-biofortified butter is a novel source of -3 PUFA, which potentiates the BAT thermogenic function.
Topics: Adipose Tissue, Brown; Animals; Butter; Diet, High-Fat; Fatty Acids; Fatty Acids, Omega-3; Food, Fortified; Lipid Metabolism; Mice; Mice, Inbred C57BL; Thermogenesis; alpha-Linolenic Acid
PubMed: 31947716
DOI: 10.3390/nu12010136 -
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 -
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 -
Advances in Nutrition (Bethesda, Md.) Nov 2014Our understanding of the cardiovascular disease (CVD) benefits of α-linolenic acid (ALA, 18:3n-3) has advanced markedly during the past decade. It is now evident that... (Comparative Study)
Comparative Study Review
Our understanding of the cardiovascular disease (CVD) benefits of α-linolenic acid (ALA, 18:3n-3) has advanced markedly during the past decade. It is now evident that ALA benefits CVD risk. The expansion of the ALA evidence base has occurred in parallel with ongoing research on eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) and CVD. The available evidence enables comparisons to be made for ALA vs. EPA + DHA for CVD risk reduction. The epidemiologic evidence suggests comparable benefits of plant-based and marine-derived n-3 (omega-3) PUFAs. The clinical trial evidence for ALA is not as extensive; however, there have been CVD event benefits reported. Those that have been reported for EPA + DHA are stronger because only EPA + DHA differed between the treatment and control groups, whereas in the ALA studies there were diet differences beyond ALA between the treatment and control groups. Despite this, the evidence suggests many comparable CVD benefits of ALA vs. EPA + DHA. Thus, we believe that it is time to revisit what the contemporary dietary recommendation should be for ALA to decrease the risk of CVD. Our perspective is that increasing dietary ALA will decrease CVD risk; however, randomized controlled clinical trials are necessary to confirm this and to determine what the recommendation should be. With a stronger evidence base, the nutrition community will be better positioned to revise the dietary recommendation for ALA for CVD risk reduction.
Topics: Cardiovascular Diseases; Diet; Dietary Supplements; Docosahexaenoic Acids; Eicosapentaenoic Acid; Evidence-Based Medicine; Humans; Inflammation; Meta-Analysis as Topic; Observational Studies as Topic; Randomized Controlled Trials as Topic; Recommended Dietary Allowances; alpha-Linolenic Acid
PubMed: 25398754
DOI: 10.3945/an.114.005850 -
The Journal of Physiology Jul 2017α-linolenic acid (ALA) and exercise training both attenuate hyperlipidaemia-related cardiovascular derangements, however, there is a paucity of information pertaining...
KEY POINTS
α-linolenic acid (ALA) and exercise training both attenuate hyperlipidaemia-related cardiovascular derangements, however, there is a paucity of information pertaining to their mechanisms of action when combined. We investigated both the independent and combined effects of exercise training and ALA consumption in obese Zucker rats, aiming to determine the potential for additive improvements in cardiovascular function. ALA and exercise training independently improved cardiac output, end-diastolic volume, left ventricular fibrosis and mean blood pressure following a 4 week intervention. Combining ALA and endurance exercise yielded greater improvements in these parameters, independent of changes in markers of oxidative stress or endogenous anti-oxidants. We postulate that divergent mechanisms of action may explain these changes: ALA increases peripheral vasodilation, and exercise training stimulates angiogenesis.
ABSTRACT
Although α-linolenic acid (ALA) and endurance exercise training independently attenuate hyperlipidaemia-related cardiovascular derangements, there is a paucity of information pertaining to their mechanisms of action and efficacy when combined as a preventative therapeutic approach. Therefore, we used obese Zucker rats to investigate the independent and combined effects of these interventions on cardiovascular disease. Specifically, animals were randomly assigned to one of the following groups: control diet-sedentary, ALA supplemented-sedentary, control diet-exercise trained or ALA supplemented-exercise trained. Following a 4 week intervention, although the independent and combined effects of ALA and exercise reduced (P < 0.05) the serum free/esterified cholesterol ratio, only the ALA supplemented-exercise trained animals displayed a reduction in the content of both serum free and esterified cholesterol. Moreover, although ALA and endurance training individually increased cardiac output, stroke volume and end-diastolic volume, as well as reduced left ventricle fibrosis, mean blood pressure and total peripheral resistance, these responses were all greater following the combined intervention (ALA supplemented-exercise trained). These effects occurred independent of changes in oxidative phosphorylation proteins, markers of oxidative stress or endogenous anti-oxidant capacity. We propose that the beneficial effects of a combined intervention occur as a result of divergent mechanisms of action elicited by ALA and endurance exercise because only exercise training increased the capillary content in the left ventricle and skeletal muscle, and tended to decrease protein carbonylation in the left ventricle (P = 0.06). Taken together, our data indicate that combining ALA and endurance exercise provides additional improvements in cardiovascular disease risk reduction compared to singular interventions in the obese Zucker rat.
Topics: Animals; Blood Pressure; Cardiovascular Diseases; Cholesterol; Diastole; Exercise Therapy; Heart Rate; Male; Obesity; Physical Conditioning, Animal; Rats; Rats, Zucker; alpha-Linolenic Acid
PubMed: 28345766
DOI: 10.1113/JP274036 -
International Journal of Molecular... Sep 2023The objective of this meta-analysis was to examine the impact of a low-ratio linoleic acid/α-linolenic acid (LA/ALA) diet on the glycemic profile of adults. A... (Meta-Analysis)
Meta-Analysis Review
The objective of this meta-analysis was to examine the impact of a low-ratio linoleic acid/α-linolenic acid (LA/ALA) diet on the glycemic profile of adults. A comprehensive search was performed across four databases (Web of Science, Scopus, Embase, and PubMed) to evaluate the influence of the low-ratio LA/ALA. Relevant references were screened up until February 2023. Intervention effects were analyzed by calculating change values as weighted mean differences (WMD) and 95% confidence intervals (CI) using fixed-effects models. Additionally, subgroup analysis and meta-regression were employed to investigate potential sources of heterogeneity. Twenty-one randomized controlled trials (RCTs) were included, and the low-ratio LA/ALA diet had no significant effect on fasting blood sugar (FBS, WMD: 0.00 mmol/L, 95% CI: -0.06, 0.06, = 0.989, I = 0.0%), insulin levels (WMD: 0.20 μIU/mL, 95% CI: -0.23, 0.63, = 0.360, I = 3.2%), homeostatic model assessment insulin resistance (HOMA-IR, WMD: 0.09, 95% CI: -0.06, 0.23, = 0.243, I = 0.0%), and hemoglobin A1c (HbA1c, WMD: -0.01%, 95% CI: -0.07, 0.06, = 0.836, I = 0.0%). Based on subgroup analyses, it was observed that the impact of a low-ratio LA/ALA diet on elevated plasma insulin (WMD: 1.31 μIU/mL, 95% CI: 0.08, 2.54, = 0.037, I = 32.0%) and HOMA-IR (WMD: 0.47, 95% CI: 0.10, 0.84, = 0.012, I = 0.0%) levels exhibited greater prominence in North America compared to Asian and European countries. Publication bias was not detected for FBS, insulin, HOMA-IR, and HbA1c levels according to the Begg and Egger tests. Furthermore, the conducted sensitivity analyses indicated stability, as the effects of the low-ratio LA/ALA diet on various glycemic and related metrics remained unchanged even after removing individual studies. Overall, based on the available studies, it can be concluded that the low-ratio LA/ALA diet has limited impact on blood glucose-related biomarker levels.
Topics: Adult; Humans; Glycated Hemoglobin; Linoleic Acid; alpha-Linolenic Acid; Glucose; Insulin
PubMed: 37762686
DOI: 10.3390/ijms241814383 -
Maternal & Child Nutrition Apr 2011Over the past two decades, there has been a marked shift in the fatty acid composition of the diets of industrialized nations towards increased intake of the n-6 fatty... (Review)
Review
Conversion of linoleic acid and alpha-linolenic acid to long-chain polyunsaturated fatty acids (LCPUFAs), with a focus on pregnancy, lactation and the first 2 years of life.
Over the past two decades, there has been a marked shift in the fatty acid composition of the diets of industrialized nations towards increased intake of the n-6 fatty acid linoleic acid (LA, 18:2n-6), largely as a result of the replacement of saturated fats with plant-based polyunsaturated fatty acid (PUFA). While health agencies internationally continue to advocate for high n-6 PUFA intake combined with increased intakes of preformed n-3 long-chain PUFAs (LCPUFA) docosahexaenoic acid (DHA, 22:6n-3) and eicosapentaenoic acid (EPA, 20:5n-3) to reduce the incidence of cardiovascular disease (CVD), there are questions as to whether this is the best approach. LA competes with alpha-linolenic acid (18:3n-3) for endogenous conversion to the LC derivatives EPA and DHA, and LA also inhibits incorporation of DHA and EPA into tissues. Thus, high-LA levels in the diet generally result in low n-3 LCPUFA status. Pregnancy and infancy are developmental periods during which the fatty acid supply is particularly critical. The importance of an adequate supply of n-3 LCPUFA for ensuring optimal development of infant brain and visual systems is well established, and there is now evidence that the supply of n-3 LCPUFA also influences a range of growth, metabolic and immune outcomes in childhood. This review will re-evaluate the health benefits of modern Western diets and pose the question of whether the introduction of similar diets to nations with emerging economies is the most prudent public health strategy for improving health in these populations.
Topics: Breast Feeding; Clinical Trials as Topic; Diet; Dietary Fats; Docosahexaenoic Acids; Eicosapentaenoic Acid; Female; Fish Oils; Humans; Infant; Lactation; Linoleic Acid; Milk, Human; Pregnancy; alpha-Linolenic Acid
PubMed: 21366864
DOI: 10.1111/j.1740-8709.2011.00299.x -
Food Chemistry Mar 2022Styrian pumpkin seed oil is a conditioned green-colored oil renowned for nutty smell and taste. Due to α-linolenic acid (ALA) contents below 1% of total fatty acids and...
α-Linolenic acid and product octadecanoids in Styrian pumpkin seeds and oils: How processing impacts lipidomes of fatty acid, triacylglycerol and oxylipin molecular structures.
Styrian pumpkin seed oil is a conditioned green-colored oil renowned for nutty smell and taste. Due to α-linolenic acid (ALA) contents below 1% of total fatty acids and the prospect of nutritional health claims based on its potential oxidation products, we investigated the fate of ALA and product oxylipins in the course of down-stream processing of seeds and in oils. Lipidomic analyses with Lipid Data Analyzer 2.8.1 revealed: Processing did not change (1) main fatty acid composition in the oils, (2) amounts of triacylglycerol species, (3) structures of triacylglycerol molecular species containing ALA. (4) Minor precursor ALA in fresh Styrian and normal pumpkins produced 6 product phytoprostanes in either cultivar, quantitatively more in the latter. (5) In oil samples 7 phytoprostanes and 2 phytofurans were detected. The latter two are specific for their presence in pumpkin seed oils, of note, quantitatively more in conditioned oils than in cold-pressed native oils.
Topics: Cucurbita; Fatty Acids; Lipidomics; Molecular Structure; Oxylipins; Plant Oils; Seeds; Triglycerides; alpha-Linolenic Acid
PubMed: 34600364
DOI: 10.1016/j.foodchem.2021.131194 -
Medicine May 2017Polyunsaturated fats (PUFAs) have been shown to reduce type 2 diabetes (T2DM) risk and improve insulin responsiveness in T2DM subjects, but whether the plant sources of... (Meta-Analysis)
Meta-Analysis Review
The effect of alpha-linolenic acid on glycemic control in individuals with type 2 diabetes: A systematic review and meta-analysis of randomized controlled clinical trials.
BACKGROUND
Polyunsaturated fats (PUFAs) have been shown to reduce type 2 diabetes (T2DM) risk and improve insulin responsiveness in T2DM subjects, but whether the plant sources of omega-3 PUFA (alpha-linolenic acid [ALA]) have an effect on glycemic control requires further investigation.
METHODS
The parameters of interest were glycated hemoglobin (HbA1c), fasting blood glucose (FBG), fasting blood insulin (FBI), homeostatic model assessment for insulin resistance (HOMA-IR), fructosamine, and glycated albumin. A comprehensive search was conducted with MEDLINE, Embase, CINAHL, and Cochrane. Eligible studies included randomized controlled trials (RCTs) ≥1 month in duration that compared diets enriched in ALA with usual diets on glycemic parameters. For each study, the risk of bias as well as the study quality was assessed. Using the statistical software RevMan (v5.3), data were pooled using the generic inverse method with random effects model, and final results were expressed as mean differences (MD) with 95% confidence intervals (CI). Heterogeneity was assessed by the Cochran Q statistic and quantified by the I statistic.
RESULTS
A total of 8 trials (N = 212) were included in the meta-analysis. Compared to a control diet, a median dose of 4.4 g/day of ALA intake for a median duration of 3 months did not affect HbA1c (%) (MD = -.01; [95%: -.32, .31], P = .96). A median ALA dose of 5.4 g/day did not lower FBG (MD = .07; [95% CI: -.61, .76], P = .84) or FBI (MD = 7.03, [95% CI: -5.84, 19.89], P = .28). Summary effect estimates were generally compromised by considerable and unexplained heterogeneity (I ≥75%). In the subgroup analysis of continuous predictors, a reduction in HbA1c (%) and FBG (mmol/L) was significantly associated with an increased intake of ALA. Further adjustment for Publication Bias using Duval and Tweedie's trim-and-fill analysis provided an adjusted, significant MD of -.25 (95% CI: -.38, -.12; P <.001) for HbA1c (%).
CONCLUSIONS
ALA-enriched diets did not affect HbA1c, FBG, or FBI. The scarce number of existing RCTs and the presence of heterogeneity in our meta-analysis limit the ability to make firm conclusions about ALA in T2DM management. The potential for ALA to have dose-dependent effects warrants further research in this area.
Topics: Diabetes Mellitus, Type 2; Humans; Randomized Controlled Trials as Topic; alpha-Linolenic Acid
PubMed: 28538363
DOI: 10.1097/MD.0000000000006531 -
The Journal of Biological Chemistry Jul 2023Sustainable TGF-β1 signaling drives organ fibrogenesis. However, the cellular adaptation to maintain TGF-β1 signaling remains unclear. In this study, we revealed that...
Sustainable TGF-β1 signaling drives organ fibrogenesis. However, the cellular adaptation to maintain TGF-β1 signaling remains unclear. In this study, we revealed that dietary folate restriction promoted the resolution of liver fibrosis in mice with nonalcoholic steatohepatitis. In activated hepatic stellate cells, folate shifted toward mitochondrial metabolism to sustain TGF-β1 signaling. Mechanistically, nontargeted metabolomics screening identified that α-linolenic acid (ALA) is exhausted by mitochondrial folate metabolism in activated hepatic stellate cells. Knocking down serine hydroxymethyltransferase 2 increases the bioconversion of ALA to docosahexaenoic acid, which inhibits TGF-β1 signaling. Finally, blocking mitochondrial folate metabolism promoted liver fibrosis resolution in nonalcoholic steatohepatitis mice. In conclusion, mitochondrial folate metabolism/ALA exhaustion/TGF-βR1 reproduction is a feedforward signaling to sustain profibrotic TGF-β1 signaling, and targeting mitochondrial folate metabolism is a promising strategy to enforce liver fibrosis resolution.
Topics: Animals; Mice; alpha-Linolenic Acid; Hepatic Stellate Cells; Liver; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease; Transforming Growth Factor beta1; Folic Acid; Mitochondria; Folic Acid Deficiency; Signal Transduction; Feedback, Physiological
PubMed: 37307917
DOI: 10.1016/j.jbc.2023.104909