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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 -
Journal of the American Medical... Oct 2020Neurocognitive function may be influenced by polyunsaturated fat intake. Many older adults consume omega-3 supplements hoping to prevent cognitive decline. We assessed... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Neurocognitive function may be influenced by polyunsaturated fat intake. Many older adults consume omega-3 supplements hoping to prevent cognitive decline. We assessed effects of increasing omega-3, omega-6, or total polyunsaturated fats on new neurocognitive illness and cognition.
DESIGN AND INCLUSION CRITERIA
We carried out a systematic review and meta-analysis of randomized controlled trials (RCTs) in adults, with duration ≥24 weeks, assessing effects of higher vs lower omega-3, omega-6, or total polyunsaturated fats and outcomes: new neurocognitive illness, newly impaired cognition, and/or continuous measures of cognition.
METHODS
We searched MEDLINE, Embase, Cochrane CENTRAL, and trials registers (final update of ongoing trials December 2018). We duplicated screening, data extraction, and risk of bias assessment. Neurocognitive measures were grouped to enable random effects meta-analysis. GRADE assessment, sensitivity analyses, and subgrouping by dose, duration, type of intervention, and replacement were used to interrogate our findings.
RESULTS
Searches generated 37,810 hits, from which we included 38 RCTs (41 comparisons, 49,757 participants). Meta-analysis suggested no or very little effect of long-chain omega-3 on new neurocognitive illness [risk ratio (RR) 0.98, 95% confidence interval (CI) 0.87-1.10, 6 RCTs, 33,496 participants, I 36%), new cognitive impairment (RR 0.99, 95% CI 0.92-1.06, 5 RCTs, 33,296 participants, I 0%) or global cognition assessed using the Mini-Mental State Examination (MD 0.10, 95% CI 0.03-0.16, 13 RCTs, 14,851 participants, I 0%), all moderate-quality evidence. Effects did not differ with sensitivity analyses, and we found no differential effects by dose, duration, intervention type, or replacement. Effects of increasing α-linolenic acid, omega-6, or total PUFA were unclear.
CONCLUSIONS
This extensive trial data set enabled assessment of effects on neurocognitive illness and cognitive decline not previously adequately assessed. Long-chain omega-3 probably has little or no effect on new neurocognitive outcomes or cognitive impairment.
IMPLICATIONS
Long-chain omega-3 supplements do not help older adults protect against cognitive decline.
Topics: Aged; Cardiovascular Diseases; Cognition; Humans; Primary Prevention; Randomized Controlled Trials as Topic; Secondary Prevention
PubMed: 32305302
DOI: 10.1016/j.jamda.2020.02.022 -
Annals of Nutrition & Metabolism 2017Earlier reviews indicated that in many countries adults, children and adolescents consume on an average less polyunsaturated fatty acids (PUFAs) than recommended by the... (Review)
Review
BACKGROUND
Earlier reviews indicated that in many countries adults, children and adolescents consume on an average less polyunsaturated fatty acids (PUFAs) than recommended by the Food and Agriculture Organisation/World Health Organisation.
SUMMARY
The intake of total and individual n-3 and n-6 PUFAs in European infants, children, adolescents, elderly and pregnant/lactating women was evaluated systematically.
RESULTS
The evaluations were done against recommendations of the European Food Safety Authority. Key Messages: Fifty-three studies from 17 different European countries reported an intake of total n-3 and n-6 PUFAs and/or individual n-3 or n-6 PUFAs in at least one of the specific population groups: 10 in pregnant women, 4 in lactating women, 3 in infants 6-12 months, 6 in children 1-3 years, 11 in children 4-9 years, 8 in adolescents 10-18 years and 11 in elderly >65 years. Mean linoleic acid intake was within the recommendation (4 energy percentage [E%]) in 52% of the countries, with inadequate intakes more likely in lactating women, adolescents and elderly. Mean α-linolenic acid intake was within the recommendation (0.5 E%) in 77% of the countries. In 26% of the countries, mean eicosapentaenoic acid and/or docosahexaenoic acid intake was as recommended. These results indicate that intake of n-3 and n-6 PUFAs may be suboptimal in specific population groups in Europe.
Topics: Adolescent; Aged; Child; Child, Preschool; Dietary Fats, Unsaturated; Europe; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Female; Humans; Infant; Lactation; Male; Milk, Human; Nutrition Policy; Pregnancy
PubMed: 28190013
DOI: 10.1159/000456723 -
Cancers May 2020Several immunotherapy agents are the standard of care of many solid malignancies. Nevertheless, the majority of patients do not benefit from the currently available... (Review)
Review
Several immunotherapy agents are the standard of care of many solid malignancies. Nevertheless, the majority of patients do not benefit from the currently available immunotherapies. It is therefore of paramount importance to identify the prognostic and predictive factors of tumor response/resistance and to design effective therapeutic strategies to overcome primary resistance and improve the efficacy of immunotherapy. The aim of this review is to underline the influence of the tumor and host metabolism on the antitumor immune response and to discuss possible strategies to improve the efficacy of available treatments by targeting the specific metabolic pathways in tumors or immune cells and by modifying patients' nutritional statuses. A systematic search of the Medline and EMBASE databases was carried out to identify scientific papers published until February 2020, which reported original research articles on the influence of tumor or host metabolism on antitumor immune response. The literature data showed the key role of glycolysis and mitochondrial oxidative phosphorylation, arginine, tryptophan, glutamine, lipid metabolism and microbiome on immune cell function. Moreover, specific nutritional behaviors, such as a low dietary intake of vitamin C, low glycemic index and alpha-linolenic acid, eicosapentenoic acid, docosahexaenoic acid, ornithine ketoglutarate, tryptophan and probiotic supplementation were associated with the potential clinical benefits from the currently available immunotherapies.
PubMed: 32375310
DOI: 10.3390/cancers12051153 -
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 Cochrane Database of Systematic... Mar 2018Antipsychotic (neuroleptic) medication is used extensively to treat people with chronic mental illnesses. Its use, however, is associated with adverse effects, including... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antipsychotic (neuroleptic) medication is used extensively to treat people with chronic mental illnesses. Its use, however, is associated with adverse effects, including movement disorders such as tardive dyskinesia (TD) - a problem often seen as repetitive involuntary movements around the mouth and face. This review, one in a series examining the treatment of TD, covers miscellaneous treatments not covered elsewhere.
OBJECTIVES
To determine whether drugs, hormone-, dietary-, or herb-supplements not covered in other Cochrane reviews on TD treatments, surgical interventions, electroconvulsive therapy, and mind-body therapies were effective and safe for people with antipsychotic-induced TD.
SEARCH METHODS
We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials including trial registers (16 July 2015 and 26 April 2017), inspected references of all identified studies for further trials and contacted authors of trials for additional information.
SELECTION CRITERIA
We included reports if they were randomised controlled trials (RCTs) dealing with people with antipsychotic-induced TD and schizophrenia or other chronic mental illnesses who remained on their antipsychotic medication and had been randomly allocated to the interventions listed above versus placebo, no intervention, or any other intervention.
DATA COLLECTION AND ANALYSIS
We independently extracted data from these trials and we estimated risk ratios (RR) or mean differences (MD), with 95% confidence intervals (CIs). We assumed that people who left early had no improvement. We assessed risk of bias and created 'Summary of findings' tables using GRADE.
MAIN RESULTS
We included 31 RCTs of 24 interventions with 1278 participants; 22 of these trials were newly included in this 2017 update. Five trials are awaiting classification and seven trials are ongoing. All participants were adults with chronic psychiatric disorders, mostly schizophrenia, and antipsychotic-induced TD. Studies were primarily of short (three to six6 weeks) duration with small samples size (10 to 157 participants), and most (61%) were published more than 20 years ago. The overall risk of bias in these studies was unclear, mainly due to poor reporting of allocation concealment, generation of the sequence, and blinding.Nineteen of the 31 included studies reported on the primary outcome 'No clinically important improvement in TD symptoms'. Two studies found moderate-quality evidence of a benefit of the intervention compared with placebo: valbenazine (RR 0.63, 95% CI 0.46 to 0.86, 1 RCT, n = 92) and extract of Ginkgo biloba (RR 0.88, 95% CI 0.81 to 0.96, 1 RCT, n = 157), respectively. However, due to small sample sizes we cannot be certain of these effects.We consider the results for the remaining interventions to be inconclusive: Low- to very low-quality evidence of a benefit was found for buspirone (RR 0.53, 95% CI 0.33 to 0.84, 1 RCT, n = 42), dihydrogenated ergot alkaloids (RR 0.45, 95% CI 0.21 to 0.97, 1 RCT, n = 28), hypnosis or relaxation, (RR 0.45, 95% CI 0.21 to 0.94, 1 study, n = 15), pemoline (RR 0.48, 95% CI 0.29 to 0.77, 1 RCT, n = 46), promethazine (RR 0.24, 95% CI 0.11 to 0.55, 1 RCT, n = 34), insulin (RR 0.52, 95% CI 0.29 to 0.96, 1 RCT, n = 20), branched chain amino acids (RR 0.79, 95% CI 0.63 to 1.00, 1 RCT, n = 52), and isocarboxazid (RR 0.24, 95% CI 0.08 to 0.71, 1 RCT, n = 20). There was low- to very low-certainty evidence of no difference between intervention and placebo or no treatment for the following interventions: melatonin (RR 0.89, 95% CI 0.71 to 1.12, 2 RCTs, n = 32), lithium (RR 1.59, 95% CI 0.79 to 3.23, 1 RCT, n = 11), ritanserin (RR 1.00, 95% CI 0.70 to 1.43, 1 RCT, n = 10), selegiline (RR 1.37, 95% CI 0.96 to 1.94, 1 RCT, n = 33), oestrogen (RR 1.18, 95% CI 0.76 to 1.83, 1 RCT, n = 12), and gamma-linolenic acid (RR 1.00, 95% CI 0.69 to 1.45, 1 RCT, n = 16).None of the included studies reported on the other primary outcome, 'no clinically significant extrapyramidal adverse effects'.
AUTHORS' CONCLUSIONS
This review has found that the use of valbenazine or extract of Ginkgo biloba may be effective in relieving the symptoms of tardive dyskinesia. However, since only one RCT has investigated each one of these compounds, we are awaiting results from ongoing trials to confirm these results. Results for the remaining interventions covered in this review must be considered inconclusive and these compounds probably should only be used within the context of a well-designed evaluative study.
Topics: Adrenergic Uptake Inhibitors; Adult; Anti-Anxiety Agents; Antipsychotic Agents; Dihydroergotoxine; Dyskinesia, Drug-Induced; Ginkgo biloba; Humans; Hypnosis; Plant Extracts; Randomized Controlled Trials as Topic; Relaxation Therapy; Tetrabenazine; Valine
PubMed: 29552749
DOI: 10.1002/14651858.CD000208.pub2 -
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 -
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 -
Food Science & Nutrition Jan 2022Bone metabolism is a complicated process, which involves bone modeling and remodeling. If this process is unbalanced, bone loss and resultant osteoporosis might occur.... (Review)
Review
Bone metabolism is a complicated process, which involves bone modeling and remodeling. If this process is unbalanced, bone loss and resultant osteoporosis might occur. Recently, nutrition supplementations such as n-3 polyunsaturated fatty acids (PUFAs) are considered to be used on improving the bone metabolism and reducing the risk of osteoporosis. To more precisely assess the effects of n-3 PUFA supplementation on bone mass and clarify its potential mechanism, we have conducted a systematic review and meta-analysis. Based on the strict inclusion and exclusion criteria, 12 articles were included in this meta-analysis. The results in articles show that n-3 PUFAs could slightly enhance the level of bone mineral density (BMD) (0.005 g/cm; 95% CI, 0.000-0.010) ( = 7), which was the primary outcome for the research in comparison with the control group. In addition, the results also illustrate that the increasing effect on BMD (0.024 g/cm; 95% CI, 0.020-0.028) became more significant for postmenopausal women. N-3 PUFAs had no significance on the level of bone-specific alkaline phosphatase (BALP) (-0.24 µg/L; 95% CI, -0.86 to 0.39) and osteocalcin (-0.63 μg/L; 95% CI, -1.84 to 0.57) ( = 5), which are the specific markers of bone formation. When compared with the eicosapentaenoic acid + docosahexaenoic acid supplementation, the supplementation form of α-linolenic acid significantly increased the content of BALP (0.396 µg/L; 95% CI, 0.069-0.724). The effects of n-3 PUFAs on bone resorption biomarkers containing type I collagen cross-linked C-terminal peptide (CTX) and type I collagen cross-linked N-terminal peptide (NTX) are considered and used in our study. Results indicated that participants who received n-3 PUFAs significantly decreased the level of CTX in the human body (-0.367 μg/L; 95% CI, -0.726 to -0.007) ( = 4). However, there was no significant difference in NTX levels in humans after supplementation with n-3 PUFA (-1.744 µg/L; 95% CI, -3.970-0.481) ( = 3). For postmenopausal women, it presented a significant decreasing level of CTX (-0.393 µg/L; 95% CI, -0.651 to -0.135) and NTX (-2.082 µg/L; 95% CI, -2.970 to -1.195) within their bodies. In conclusion, these findings suggested that n-3 PUFAs might have a beneficial effect on bone health, especially for α-linolenic acid supplementation form or for postmenopausal women.
PubMed: 35035917
DOI: 10.1002/fsn3.2655 -
Critical Reviews in Food Science and... Apr 2023Conjugated linolenic acid (CLnA) is a mixture of octadecenoic acid with multiple positional and geometric isomers (including four 9, 11, 13-C18:3 isomers and three 8,...
Conjugated linolenic acid (CLnA) is a mixture of octadecenoic acid with multiple positional and geometric isomers (including four 9, 11, 13-C18:3 isomers and three 8, 10, 12-C18:3 isomers) that is mainly present in plant seeds. In recent years, CLnA has shown many promising health benefits with the deepening of research, but the metabolic characteristics, physiological function differences and mechanisms of different isomers are relatively complex. In this article, the metabolic characteristics of CLnA were firstly reviewed, with focus on its conversion, catabolism and anabolism. Then the possible mechanisms of CLnA exerting biological effects were summarized and analyzed from its own chemical and physical characteristics, as well as biological receptor targeting characteristics. In addition, the differences and mechanisms of different isomers of CLnA in anticancer, lipid-lowering, anti-diabetic and anti-inflammatory physiological functions were compared and summarized. The current results show that the position and cis-trans conformation of conjugated structure endow CLnA with unique physical and chemical properties, which also makes different isomers have commonalities and particularities in the regulation of metabolism and physiological functions. Corresponding the metabolic characteristics of different isomers with precise nutrition strategy will help them to play a better role in disease prevention and treatment. CLnA has the potential to be developed into food functional components and dietary nutritional supplements. The advantages and mechanisms of different CLnA isomers in the clinical management of specific diseases need further study.
PubMed: 37021469
DOI: 10.1080/10408398.2023.2198006