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Critical Reviews in Food Science and... 2014Presently alpha-linolenic acid (ALA) is the most widely used vegetarian LC3PUFA, but only marginal amounts are converted into eicosapentaenoic (EPA) and docosahexaenoic... (Review)
Review
Presently alpha-linolenic acid (ALA) is the most widely used vegetarian LC3PUFA, but only marginal amounts are converted into eicosapentaenoic (EPA) and docosahexaenoic acid (DHA); both of which are strongly related to human health. Currently, fish oils represent the most prominent dietary sources of EPA and DHA; however, these are unsuitable for vegetarians. Alternative sources include flaxseed, echium, walnut, and algal oil but their conversion to EPA and DHA must be considered. The present systematic review sets out to collate information from intervention studies examining the bioavailability of alternative vegetarian long chain omega-3 (n-3) polyunsaturated fatty acids (LC3PUFA) sources. Ten key papers published over the last 10 years were identified with seven intervention studies reporting that ALA from nut and seed oils was not converted to DHA at all. Three studies showed that ingestion of micro-algae oil led to significant increases in blood erythrocyte and plasma DHA. Further work is now needed to identify optimal doses of alternative vegetarian LC3PUFAs and how these can be integrated within daily diets. The potential role of algal oils appears to be particularly promising and an area in which further research is warranted.
Topics: Biological Availability; Diet, Vegetarian; Docosahexaenoic Acids; Echium; Fatty Acids, Omega-3; Fish Oils; Functional Food; Humans; Juglans; Linseed Oil; Nuts; Plant Oils; alpha-Linolenic Acid
PubMed: 24261532
DOI: 10.1080/10408398.2011.596292 -
The American Journal of Clinical... May 2009alpha-Linolenic acid (ALA; 18:3n-3) has been associated inconsistently with an increased risk of prostate cancer. Additional studies have become available since the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
alpha-Linolenic acid (ALA; 18:3n-3) has been associated inconsistently with an increased risk of prostate cancer. Additional studies have become available since the publication of 2 previous meta-analyses.
OBJECTIVE
The objective was to review the published data on the relation between ALA and prostate cancer.
DESIGN
We conducted a systematic review to identify studies that included data on ALA and risk of prostate cancer. Data were pooled from studies that compared the highest ALA quantile with the lowest ALA quantile, and risk estimates were combined by using a random-effects model.
RESULTS
The relation between ALA and prostate cancer is inconsistent across studies. We pooled data from 8 case-control and 8 prospective studies. The summary estimate revealed that high ALA dietary intakes or tissue concentrations are weakly associated with prostate cancer risk (relative risk [RR]: 1.20; 95% CI: 1.01, 1.43). When examined by study type (ie, retrospective compared with prospective or dietary ALA compared with tissue concentration) or by decade of publication, only the 6 studies examining blood or tissue ALA concentrations revealed a statistically significant association. With the exception of these studies, there was significant heterogeneity and evidence of publication bias. After adjustment for publication bias, there was no association between ALA and prostate cancer (RR: 0.96; 95% CI: 0.79, 1.17).
CONCLUSIONS
Studies examining the relation between ALA and prostate cancer have produced inconsistent findings. High ALA intakes or high blood and adipose tissue concentrations of ALA may be associated with a small increased risk of prostate cancer. However, these conclusions are qualified because of the heterogeneity across studies and the likelihood of publication bias.
Topics: Adipose Tissue; Case-Control Studies; Humans; Male; Odds Ratio; Prospective Studies; Prostatic Neoplasms; Reproducibility of Results; Risk Factors; alpha-Linolenic Acid
PubMed: 19321563
DOI: 10.3945/ajcn.2009.26736E -
Clinical Nutrition (Edinburgh, Scotland) Jun 2022Inflammation and dyslipidemia are traditional risk factors and well-known causes of morbidity and mortality in chronic kidney disease (CKD). Alpha-linolenic acid (ALA),... (Meta-Analysis)
Meta-Analysis
Effects of supplementation with vegetable sources of alpha-linolenic acid (ALA) on inflammatory markers and lipid profile in individuals with chronic kidney disease: A systematic review and meta-analysis.
BACKGROUND AND AIMS
Inflammation and dyslipidemia are traditional risk factors and well-known causes of morbidity and mortality in chronic kidney disease (CKD). Alpha-linolenic acid (ALA), an essential fatty acid mainly found in vegetable sources, has been associated with anti-inflammatory effects and improving lipid profile. This systematic review and meta-analysis investigate the effects of supplementation with vegetable sources of ALA on inflammatory marker and lipid profile in individuals with CKD.
METHODS
This review included studies with adult or elderly patients with CKD, including those receiving dialysis, using oral supplementation or food or combined interventions containing vegetable sources of ALA. All studies were randomized trials and The Cochrane Collaboration's tool was use for assessing risk of bias.
RESULTS
19 studies provided data for meta-analyses. ALA had significant effect on reducing C-reactive protein (CRP) after supplementation (WMD: -1.32; 84.5% CI, -2.35 to -0.29, P = 0.012), on the other hand, had no significant effect on total cholesterol (WMD: -2.85; 90.1% CI, -14.43 to 8.73, P = 0.629), high density lipoprotein (WMD: 1.09; 92.4% CI, -1.82 to 3.99, P = 0.463), low density lipoprotein (WMD: -3.87; 86.7% CI, -12.62 to 4.89, P = 0.387) and triglycerides (WMD: -16.42; 87.7% CI, -47.83 to 14.98, P = 0.305).
CONCLUSION
Vegetables sources of ALA showed beneficial effects on reducing inflammatory marker CRP in CKD patients but had no effect on lipid profile. Future well-designed studies are needed to investigate the effectiveness of vegetables sources of ALA, particularly in CKD.
Topics: Adult; Aged; Biomarkers; C-Reactive Protein; Dietary Supplements; Humans; Renal Dialysis; Renal Insufficiency, Chronic; Vegetables; alpha-Linolenic Acid
PubMed: 35341608
DOI: 10.1016/j.clnu.2022.02.013 -
The British Journal of Nutrition Jan 2018Previous studies show inconsistent associations between α-linolenic acid (ALA) and risk of CHD. We aimed to examine an aggregate association between ALA intake and risk... (Meta-Analysis)
Meta-Analysis Review
Previous studies show inconsistent associations between α-linolenic acid (ALA) and risk of CHD. We aimed to examine an aggregate association between ALA intake and risk of CHD, and assess for any dose-response relationship. We searched the PubMed, EMBASE and Web of Science databases for prospective cohort studies examining associations between ALA intake and CHD, including composite CHD and fatal CHD. Data were pooled using random-effects meta-analysis models, comparing the highest category of ALA intake with the lowest across studies. Subgroup analysis was conducted based on study design, geographic region, age and sex. For dose-response analyses, we used two-stage random-effects dose-response models. In all, fourteen studies of thirteen cohorts were identified and included in the meta-analysis. The pooled results showed that higher ALA intake was associated with modest reduced risk of composite CHD (risk ratios (RR)=0·91; 95 % CI 0·85, 0·97) and fatal CHD (RR=0·85; 95 % CI 0·75, 0·96). The analysis showed a J-shaped relationship between ALA intake and relative risk of composite CHD (χ 2=21·95, P<0·001). Compared with people without ALA intake, only people with ALA intake <1·4 g/d showed reduced risk of composite CHD. ALA intake was linearly associated with fatal CHD - every 1 g/d increase in ALA intake was associated with a 12 % decrease in fatal CHD risk (95 % CI -0·21, -0·04). Though a higher dietary ALA intake was associated with reduced risk of composite and fatal CHD, the excess composite CHD risk at higher ALA intakes warrants further investigation, especially through randomised controlled trials.
Topics: Adult; Aged; Cohort Studies; Coronary Disease; Diet; Dose-Response Relationship, Drug; Female; Humans; Linear Models; Male; Middle Aged; Odds Ratio; Prospective Studies; Randomized Controlled Trials as Topic; Risk Factors; alpha-Linolenic Acid
PubMed: 29355094
DOI: 10.1017/S0007114517003294 -
Foods (Basel, Switzerland) Aug 2023This meta-analysis aimed to investigate the impact of low-ratio linoleic acid/alpha-linolenic acid (LA/ALA) supplementation on the blood lipid profiles in adults. We...
This meta-analysis aimed to investigate the impact of low-ratio linoleic acid/alpha-linolenic acid (LA/ALA) supplementation on the blood lipid profiles in adults. We conducted a systematic search for relevant randomized controlled trials (RCTs) assessing the effects of low-ratio LA/ALA using databases including PubMed, Embase, Cochrane, and Web of Science, as well as screened related references up until February 2023. The intervention effects were analyzed adopting weighted mean difference (WMD) and 95% confidence interval (CI). The meta-analysis indicated that low-ratio LA/ALA supplementation decreased total cholesterol (TC, WMD: -0.09 mmol/L, 95% CI: -0.17, -0.01, = 0.031, I = 33.2%), low-density lipoprotein cholesterol (LDL-C, WMD: -0.08 mmol/L, 95% CI: -0.13, -0.02, = 0.007, I = 0.0%), and triglycerides (TG, WMD: -0.05 mmol/L, 95% CI: -0.09, 0.00, = 0.049, I = 0.0%) concentrations. There was no significant effect on high-density lipoprotein cholesterol concentration (HDL-C, WMD: -0.00 mmol/L, 95% CI: -0.02, 0.02, = 0.895, I = 0.0%). Subgroup analysis showed that low-ratio LA/ALA supplementation significantly decreased plasma TC, LDL-C, and TG concentrations when the intervention period was less than 12 weeks. In the subgroup analysis, a noteworthy decrease in both TC and LDL-C levels was observed in individuals receiving low-ratio LA/ALA supplementation in the range of 1-5. These findings suggest that this specific range could potentially be effective in reducing lipid profiles. The findings of this study provide additional evidence supporting the potential role of low-ratio LA/ALA supplementation in reducing TC, LDL-C, and TG concentrations, although no significant impact on HDL-C was observed.
PubMed: 37628004
DOI: 10.3390/foods12163005 -
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 -
Critical Reviews in Food Science and... 2021To investigate the effect of ALA intake on blood lipid profiles, including triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C),... (Meta-Analysis)
Meta-Analysis
To investigate the effect of ALA intake on blood lipid profiles, including triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very-low-density lipoprotein (VLDL-C) and ratio of TC to HDL-C. We systematically searched randomized controlled trials of ALA intervention on PubMed, Embase, Cochrane library and related references up to March 2018. The final values were calculated as weighted mean difference (WMD) by using a random effects model. Subgroup analysis and meta-regression were used to explore the source of heterogeneity. Generalized least square was performed for dose-response analysis. Forty-seven studies with 1305 individuals in the ALA arm and 1325 individuals in the control arm were identified. Compared with control group, dietary intake of ALA significantly reduced the concentrations of TG (WMD -0.101 mmol/L; 95% CI: -0.158 to -0.044 mmol/L; 0.001), TC (WMD -0.140 mmol/L; 95% CI: -0.224 to -0.056 mmol/L; 0.001), LDL-C (WMD -0.131 mmol/L; 95% CI: -0.191 to -0.071 mmol/L; 0.001), VLDL-C (WMD -0.121 mmol/L; 95% CI: -0.170 to -0.073 mmol/L; 0.001), TC/HDL-C ratio (WMD -0.165 mmol/L; 95% CI: -0.317 to -0.013 mmol/L; 0.033) and LDL-C/HDL-C ratio (WMD -0.158 mmol/L; 95% CI: -0.291 to -0.025 mmol/L; 0.02). There is no effect of ALA intake on HDL-C (WMD 0.008 mmol/L; 95% CI: -0.018 to 0.034 mmol/L; 0.541). Dose-response analysis indicated that 1 g per day increment of ALA was associated with a 0.0016 mmol/L, 0.0071 mmol/L, 0.0015 and 0.0061 mmol/L reduction in TG (95% CI: -0.0029 to -0.0002 mmol/L), TC (95% CI: -0.0085 to -0.0058 mmol/L), HDL-C (95% CI: -0.0020 to -0.0011 mmol/L) and LDL-C (95% CI: -0.0073 to -0.0049 mmol/L) levels, respectively. The effects of ALA intake on TG, TC and LDL-C concentrations were more obvious among Asian participants, and also more obvious on patients with hyperlipidemia or hyperglycemia compared to healthy individuals. Dietary ALA intervention improves blood lipid profiles by decreasing levels of TG, TC, LDL and VLDL-C. Our findings add to the evidence that increasing ALA intake could potentially prevent risk of cardiovascular diseases.
Topics: Cholesterol, HDL; Cholesterol, LDL; Humans; Lipids; Randomized Controlled Trials as Topic; Triglycerides; alpha-Linolenic Acid
PubMed: 32643951
DOI: 10.1080/10408398.2020.1790496 -
BMJ (Clinical Research Ed.) Aug 2019To assess effects of increasing omega-3, omega-6, and total polyunsaturated fatty acids (PUFA) on diabetes diagnosis and glucose metabolism. (Meta-Analysis)
Meta-Analysis
Omega-3, omega-6, and total dietary polyunsaturated fat for prevention and treatment of type 2 diabetes mellitus: systematic review and meta-analysis of randomised controlled trials.
OBJECTIVE
To assess effects of increasing omega-3, omega-6, and total polyunsaturated fatty acids (PUFA) on diabetes diagnosis and glucose metabolism.
DESIGN
Systematic review and meta-analyses.
DATA SOURCES
Medline, Embase, Cochrane CENTRAL, WHO International Clinical Trials Registry Platform, Clinicaltrials.gov, and trials in relevant systematic reviews.
ELIGIBILITY CRITERIA
Randomised controlled trials of at least 24 weeks' duration assessing effects of increasing α-linolenic acid, long chain omega-3, omega-6, or total PUFA, which collected data on diabetes diagnoses, fasting glucose or insulin, glycated haemoglobin (HbA), and/or homoeostatic model assessment for insulin resistance (HOMA-IR).
DATA SYNTHESIS
Statistical analysis included random effects meta-analyses using relative risk and mean difference, and sensitivity analyses. Funnel plots were examined and subgrouping assessed effects of intervention type, replacement, baseline risk of diabetes and use of antidiabetes drugs, trial duration, and dose. Risk of bias was assessed with the Cochrane tool and quality of evidence with GRADE.
RESULTS
83 randomised controlled trials (mainly assessing effects of supplementary long chain omega-3) were included; 10 were at low summary risk of bias. Long chain omega-3 had little or no effect on likelihood of diagnosis of diabetes (relative risk 1.00, 95% confidence interval 0.85 to 1.17; 58 643 participants, 3.7% developed diabetes) or measures of glucose metabolism (HbA mean difference -0.02%, 95% confidence interval -0.07% to 0.04%; plasma glucose 0.04, 0.02 to 0.07, mmol/L; fasting insulin 1.02, -4.34 to 6.37, pmol/L; HOMA-IR 0.06, -0.21 to 0.33). A suggestion of negative outcomes was observed when dose of supplemental long chain omega-3 was above 4.4 g/d. Effects of α-linolenic acid, omega-6, and total PUFA on diagnosis of diabetes were unclear (as the evidence was of very low quality), but little or no effect on measures of glucose metabolism was seen, except that increasing α-linolenic acid may increase fasting insulin (by about 7%). No evidence was found that the omega-3/omega-6 ratio is important for diabetes or glucose metabolism.
CONCLUSIONS
This is the most extensive systematic review of trials to date to assess effects of polyunsaturated fats on newly diagnosed diabetes and glucose metabolism, including previously unpublished data following contact with authors. Evidence suggests that increasing omega-3, omega-6, or total PUFA has little or no effect on prevention and treatment of type 2 diabetes mellitus.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42017064110.
Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 2; Dietary Fats, Unsaturated; Dietary Supplements; Fasting; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Female; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Male; Primary Prevention; Randomized Controlled Trials as Topic; Secondary Prevention
PubMed: 31434641
DOI: 10.1136/bmj.l4697 -
European Journal of Nutrition Apr 2018The aim of the current meta-analysis was to investigate the effect of increasing dietary ALA intake on the blood concentration of inflammatory markers including tumor... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
The aim of the current meta-analysis was to investigate the effect of increasing dietary ALA intake on the blood concentration of inflammatory markers including tumor necrosis factor (TNF), interleukin 6 (IL-6), C-reactive protein (CRP), soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) in adults.
METHODS
After a systemic search on PubMed, Embase, and Cochrane library and bibliographies of relevant articles, 25 randomized controlled trials that met the inclusion criteria were identified.
RESULTS
No significant effect of dietary ALA supplementation was observed on TNF (SMD: -0.03, 95% CI -0.36 to 0.29), IL-6 (SMD: -0.17, 95% CI -0.46 to 0.12), CRP (SMD: -0.06, 95% CI -0.24 to 0.12), sICAM-1 (SMD: -0.06, 95% CI -0.26 to 0.13), and sVCAM-1 (SMD: -0.24, 95% CI -0.56 to 0.09). Subgroup analysis revealed that increasing dietary ALA tends to elevate CRP concentration in healthy subjects. However, the null effect of ALA supplementation on other inflammatory markers was not changed in various subgroups, indicating that the results are stable. Meta-regression results revealed a negative relationship between the effect size on CRP and its baseline concentration. No significant publication bias was observed for all inflammatory markers as suggested by funnel plot and Begg's test.
CONCLUSION
Our meta-analysis did not find any beneficial effect of ALA supplementation on reducing inflammatory markers including TNF, IL-6, CRP, sICAM-1, and sVCAM-1. However, in healthy subjects, ALA supplementation might increase CRP concentration.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Biomarkers; C-Reactive Protein; Chronic Disease; Dietary Supplements; Evidence-Based Medicine; Humans; Inflammation Mediators; Intercellular Adhesion Molecule-1; Interleukin-6; Randomized Controlled Trials as Topic; Solubility; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1; alpha-Linolenic Acid
PubMed: 28275869
DOI: 10.1007/s00394-017-1386-2 -
Lipids Jan 2005This systematic review and meta-analysis aimed to evaluate the effect of modifying 18-carbon PUFA [18-C PUFA: alpha-linolenic acid (ALA, 18:3n-3) and linoleic acid (LA,... (Meta-Analysis)
Meta-Analysis Review
The effect of alpha-linolenic acid and linoleic acid on the growth and development of formula-fed infants: a systematic review and meta-analysis of randomized controlled trials.
This systematic review and meta-analysis aimed to evaluate the effect of modifying 18-carbon PUFA [18-C PUFA: alpha-linolenic acid (ALA, 18:3n-3) and linoleic acid (LA, 18:2n-6)] in the diets of term and preterm infants on DHA (22:6n-3) status, growth, and developmental outcomes. Only randomized controlled trials (RCT) involving formula-fed term and preterm infants, in which the 18-C PUFA composition of the formula was changed and growth or developmental outcomes were measured, were included. Differences were presented as control (standard formula) and treatment (18-C PUFA-supplemented formula). Primary analyses for term infants were 4 and 12 mon and for preterm infants 37-42 and 57 wk postmenstrual age. Five RCT involving term infants and three RCT involving preterm infants were included in the systematic review. Infants fed ALA-supplemented formula had significantly higher plasma and erythrocyte phospholipid DHA levels than control infants. There was no effect of ALA supplementation on the growth of preterm infants. In term infants, ALA supplementation was associated with increased weight and length at 12 mon, which was at least 4 mon after the end of dietary intervention. Developmental indices of term infants did not differ between groups. There was a transient improvement in the retinal function of preterm infants fed ALA-supplemented diets compared with controls. The findings suggest that ALA-supplemented diets improve the DHA status of infants. Further studies are needed to provide convincing evidence regarding the effects of ALA supplementation of formula on infant growth and development.
Topics: Body Size; Child Development; Dietary Supplements; Erythrocytes; Humans; Infant Formula; Infant, Newborn; Linoleic Acid; Phospholipids; Premature Birth; Retina; Time Factors; alpha-Linolenic Acid
PubMed: 15825825
DOI: 10.1007/s11745-005-1354-8