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The Cochrane Database of Systematic... Feb 2020Omega-3 polyunsaturated fatty acids from oily fish (long-chain omega-3 (LCn3)), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)), as well as from... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Omega-3 polyunsaturated fatty acids from oily fish (long-chain omega-3 (LCn3)), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)), as well as from plants (alpha-linolenic acid (ALA)) may benefit cardiovascular health. Guidelines recommend increasing omega-3-rich foods, and sometimes supplementation, but recent trials have not confirmed this.
OBJECTIVES
To assess the effects of increased intake of fish- and plant-based omega-3 fats for all-cause mortality, cardiovascular events, adiposity and lipids.
SEARCH METHODS
We searched CENTRAL, MEDLINE and Embase to February 2019, plus ClinicalTrials.gov and World Health Organization International Clinical Trials Registry to August 2019, with no language restrictions. We handsearched systematic review references and bibliographies and contacted trial authors.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that lasted at least 12 months and compared supplementation or advice to increase LCn3 or ALA intake, or both, versus usual or lower intake.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion, extracted data and assessed validity. We performed separate random-effects meta-analysis for ALA and LCn3 interventions, and assessed dose-response relationships through meta-regression.
MAIN RESULTS
We included 86 RCTs (162,796 participants) in this review update and found that 28 were at low summary risk of bias. Trials were of 12 to 88 months' duration and included adults at varying cardiovascular risk, mainly in high-income countries. Most trials assessed LCn3 supplementation with capsules, but some used LCn3- or ALA-rich or enriched foods or dietary advice compared to placebo or usual diet. LCn3 doses ranged from 0.5 g a day to more than 5 g a day (19 RCTs gave at least 3 g LCn3 daily). Meta-analysis and sensitivity analyses suggested little or no effect of increasing LCn3 on all-cause mortality (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.93 to 1.01; 143,693 participants; 11,297 deaths in 45 RCTs; high-certainty evidence), cardiovascular mortality (RR 0.92, 95% CI 0.86 to 0.99; 117,837 participants; 5658 deaths in 29 RCTs; moderate-certainty evidence), cardiovascular events (RR 0.96, 95% CI 0.92 to 1.01; 140,482 participants; 17,619 people experienced events in 43 RCTs; high-certainty evidence), stroke (RR 1.02, 95% CI 0.94 to 1.12; 138,888 participants; 2850 strokes in 31 RCTs; moderate-certainty evidence) or arrhythmia (RR 0.99, 95% CI 0.92 to 1.06; 77,990 participants; 4586 people experienced arrhythmia in 30 RCTs; low-certainty evidence). Increasing LCn3 may slightly reduce coronary heart disease mortality (number needed to treat for an additional beneficial outcome (NNTB) 334, RR 0.90, 95% CI 0.81 to 1.00; 127,378 participants; 3598 coronary heart disease deaths in 24 RCTs, low-certainty evidence) and coronary heart disease events (NNTB 167, RR 0.91, 95% CI 0.85 to 0.97; 134,116 participants; 8791 people experienced coronary heart disease events in 32 RCTs, low-certainty evidence). Overall, effects did not differ by trial duration or LCn3 dose in pre-planned subgrouping or meta-regression. There is little evidence of effects of eating fish. Increasing ALA intake probably makes little or no difference to all-cause mortality (RR 1.01, 95% CI 0.84 to 1.20; 19,327 participants; 459 deaths in 5 RCTs, moderate-certainty evidence),cardiovascular mortality (RR 0.96, 95% CI 0.74 to 1.25; 18,619 participants; 219 cardiovascular deaths in 4 RCTs; moderate-certainty evidence), coronary heart disease mortality (RR 0.95, 95% CI 0.72 to 1.26; 18,353 participants; 193 coronary heart disease deaths in 3 RCTs; moderate-certainty evidence) and coronary heart disease events (RR 1.00, 95% CI 0.82 to 1.22; 19,061 participants; 397 coronary heart disease events in 4 RCTs; low-certainty evidence). However, increased ALA may slightly reduce risk of cardiovascular disease events (NNTB 500, RR 0.95, 95% CI 0.83 to 1.07; but RR 0.91, 95% CI 0.79 to 1.04 in RCTs at low summary risk of bias; 19,327 participants; 884 cardiovascular disease events in 5 RCTs; low-certainty evidence), and probably slightly reduces risk of arrhythmia (NNTB 91, RR 0.73, 95% CI 0.55 to 0.97; 4912 participants; 173 events in 2 RCTs; moderate-certainty evidence). Effects on stroke are unclear. Increasing LCn3 and ALA had little or no effect on serious adverse events, adiposity, lipids and blood pressure, except increasing LCn3 reduced triglycerides by ˜15% in a dose-dependent way (high-certainty evidence).
AUTHORS' CONCLUSIONS
This is the most extensive systematic assessment of effects of omega-3 fats on cardiovascular health to date. Moderate- and low-certainty evidence suggests that increasing LCn3 slightly reduces risk of coronary heart disease mortality and events, and reduces serum triglycerides (evidence mainly from supplement trials). Increasing ALA slightly reduces risk of cardiovascular events and arrhythmia.
Topics: Adiposity; Adult; Arrhythmias, Cardiac; Cardiovascular Diseases; Cause of Death; Coronary Disease; Dietary Supplements; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Hemorrhage; Humans; Primary Prevention; Pulmonary Embolism; Randomized Controlled Trials as Topic; Regression Analysis; Secondary Prevention; Stroke; Treatment Outcome; alpha-Linolenic Acid
PubMed: 32114706
DOI: 10.1002/14651858.CD003177.pub5 -
British Journal of Cancer Apr 2020The relationship between long-chain omega-3 (LCn3), alpha-linolenic acid (ALA), omega-6 and total polyunsaturated fatty acid (PUFA) intakes and cancer risk is unclear. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The relationship between long-chain omega-3 (LCn3), alpha-linolenic acid (ALA), omega-6 and total polyunsaturated fatty acid (PUFA) intakes and cancer risk is unclear.
METHODS
We searched Medline, Embase, CENTRAL and trials registries for RCTs comparing higher with lower LCn3, ALA, omega-6 and/or total PUFA, that assessed cancers over ≥12 months. Random-effects meta-analyses, sensitivity analyses, subgrouping, risk of bias and GRADE were used.
RESULTS
We included 47 RCTs (108,194 participants). Increasing LCn3 has little or no effect on cancer diagnosis (RR1.02, 95% CI 0.98-1.07), cancer death (RR0.97, 95% CI 0.90-1.06) or breast cancer diagnosis (RR1.03, 95% CI 0.89-1.20); increasing ALA has little or no effect on cancer death (all high/moderate-quality evidence). Increasing LCn3 (NNTH 334, RR1.10, 95% CI 0.97-1.24) and ALA (NNTH 334, RR1.30, 95% CI 0.72-2.32) may slightly increase prostate cancer risk; increasing total PUFA may slightly increase risk of cancer diagnosis (NNTH 125, RR1.19, 95% CI 0.99-1.42) and cancer death (NNTH 500, RR1.10, 95% CI 0.48-2.49) but total PUFA doses were very high in some trials.
CONCLUSIONS
The most extensive systematic review to assess the effects of increasing PUFAs on cancer risk found increasing total PUFA may very slightly increase cancer risk, offset by small protective effects on cardiovascular diseases.
Topics: Fatty Acids, Omega-3; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Humans; Incidence; Neoplasms; Randomized Controlled Trials as Topic; Risk; alpha-Linolenic Acid
PubMed: 32114592
DOI: 10.1038/s41416-020-0761-6 -
Taiwanese Journal of Obstetrics &... Jan 2020The efficacy of n-3 fatty acids supplementation on the prevention of pregnancy-induced hypertension or preeclampsia remains unclear. The aim of study was to examine the... (Meta-Analysis)
Meta-Analysis
The efficacy of n-3 fatty acids supplementation on the prevention of pregnancy-induced hypertension or preeclampsia remains unclear. The aim of study was to examine the effect of supplementation with EPA, and/or DHA, and/or ALA during pregnancy on the pregnancy-induced hypertension or preeclampsia. A systematic search was performed on Scopus, PubMed, Web of Science (WoS), Cochrane Library, and Google scholar, which covered the period between 1991 and 2018. The clinical trials with any control groups (i.e. placebo or other supplementation) were selected. The whole process of meta-analysis and data analysis was done using Comprehensive Meta-Analysis (Version 2.0, Biostat). The searched keywords were: "Fatty Acids, Omega-3", "n-3 Polyunsaturated Fatty Acid" "Eicosapentaenoic Acid", "Docosahexaenoic Acids", "n-3 Polyunsaturated Fatty Acid", "n-3 PUFAs", "alpha-Linolenic Acid", "fish oil", "Nuts", "nutrient", or their synonyms "pregnancy induced hypertension" and preeclampsia. In addition, some key journals, according to Scopus report and the references of the original and review articles, were manually searched for possible related studies. The meta-analysis of the 14 comparisons demonstrated that n-3 fatty acids supplementation played a protective role against the risk of preeclampsia (RR, 0.82; 95% CI, 0.70-0.97; p = 0.024; I2 = 19.0%). The analysis of the 10 comparisons revealed that n-3 fatty acid supplements for pregnant women did not mitigate the risk of pregnancy-induced hypertension (RR, 0.98; 95% CI, 0.90-1.07; p = 0.652; I2 = 0%). The n-3 fatty acid supplements are an effective strategy to prevent the incidence of preeclampsia in women with low-risk pregnancies.
Topics: Adult; Dietary Supplements; Fatty Acids, Omega-3; Female; Humans; Hypertension, Pregnancy-Induced; Maternal Nutritional Physiological Phenomena; Pre-Eclampsia; Pregnancy; Prenatal Care; Treatment Outcome
PubMed: 32039806
DOI: 10.1016/j.tjog.2019.11.002 -
Nutrition Reviews Aug 2020Polyunsaturated fatty acids (PUFA) are important during pregnancy for fetal development and child health outcomes. The fatty acid desaturase (FADS) genes also influence...
CONTEXT
Polyunsaturated fatty acids (PUFA) are important during pregnancy for fetal development and child health outcomes. The fatty acid desaturase (FADS) genes also influence PUFA status, with the FADS genes controlling how much product (eg, arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid) is metabolized from the precursor molecules linoleic acid and α-linolenic acid.
OBJECTIVE
The current review discusses the influence of FADS genotype on PUFA status of pregnant women, breast milk, and children, and also how FADS may influence child health outcomes.
DATA SOURCES
The Ovid Medline, Scopus, Embase, Cochrane Library, CINAHL Plus, PubMed and Web of Science databases were searched from their inception to September 2018.
DATA EXTRACTION
Eligible studies reported FADS genotype and blood concentrations of PUFA during pregnancy, in childhood, breast milk concentrations of PUFA or child health outcomes.
DATA ANALYSIS
In pregnant and lactating women, minor allele carriers have higher concentrations of linoleic acid and α-linolenic acid, and lower concentrations of arachidonic acid, in blood and breast milk, respectively. In children, FADS genotype influences PUFA status in the same manner and may impact child outcomes such as cognition and allergies; however, the direction of effects for the evidence to date is not consistent.
CONCLUSION
Further studies are needed to further investigate associations between FADS and outcomes, as well as the diet-gene interaction.
Topics: Adolescent; Adult; Alleles; Arachidonic Acid; Child; Child Health; Child, Preschool; Docosahexaenoic Acids; Fatty Acid Desaturases; Fatty Acids, Unsaturated; Female; Humans; Infant; Linoleic Acid; Milk, Human; Polymorphism, Single Nucleotide; Pregnancy; Young Adult
PubMed: 31943072
DOI: 10.1093/nutrit/nuz086 -
The Cochrane Database of Systematic... Dec 2019Polyunsaturated fatty acid (PUFA) supplements, involving omega-3 and/or omega-6 components, have been proposed as a therapy for dry eye. Omega-3 PUFAs exist in both... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Polyunsaturated fatty acid (PUFA) supplements, involving omega-3 and/or omega-6 components, have been proposed as a therapy for dry eye. Omega-3 PUFAs exist in both short- (alpha-linolenic acid [ALA]) and long-chain (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) forms, which largely derive from certain plant- and marine-based foods respectively. Omega-6 PUFAs are present in some vegetable oils, meats, and other animal products.
OBJECTIVES
To assess the effects of omega-3 and omega-6 polyunsaturated fatty acid (PUFA) supplements on dry eye signs and symptoms.
SEARCH METHODS
CENTRAL, Medline, Embase, two other databases and three trial registries were searched in February 2018, together with reference checking. A top-up search was conducted in October 2019, but the results have not yet been incorporated.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) involving dry eye participants, in which omega-3 and/or omega-6 supplements were compared with a placebo/control supplement, artificial tears, or no treatment. We included head-to-head trials comparing different forms or doses of PUFAs.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methods and assessed the certainty of the evidence using GRADE.
MAIN RESULTS
We included 34 RCTs, involving 4314 adult participants from 13 countries with dry eye of variable severity and etiology. Follow-up ranged from one to 12 months. Nine (26.5%) studies had published protocols and/or were registered. Over half of studies had high risk of bias in one or more domains. Long-chain omega-3 (EPA and DHA) versus placebo or no treatment (10 RCTs) We found low certainty evidence that there may be little to no reduction in dry eye symptoms with long-chain omega-3 versus placebo (four studies, 677 participants; mean difference [MD] -2.47, 95% confidence interval [CI] -5.14 to 0.19 units). We found moderate certainty evidence for a probable benefit of long-chain omega-3 supplements in increasing aqueous tear production relative to placebo (six studies, 1704 participants; MD 0.68, 95% CI 0.26 to 1.09 mm/5 min using the Schirmer test), although we did not judge this difference to be clinically meaningful. We found low certainty evidence for a possible reduction in tear osmolarity (one study, 54 participants; MD -17.71, 95% CI -28.07 to -7.35 mOsmol/L). Heterogeneity was too substantial to pool data on tear break-up time (TBUT) and adverse effects. Combined omega-3 and omega-6 versus placebo (four RCTs) For symptoms (low certainty) and ocular surface staining (moderate certainty), data from the four included trials could not be meta-analyzed, and thus effects on these outcomes were unclear. For the Schirmer test, we found moderate certainty evidence that there was no intergroup difference (four studies, 455 participants; MD: 0.66, 95% CI -0.45 to 1.77 mm/5 min). There was moderate certainty for a probable improvement in TBUT with the PUFA intervention relative to placebo (four studies, 455 participants; MD 0.55, 95% CI 0.04 to 1.07 seconds). Effects on tear osmolarity and adverse events were unclear, with data only available from a single small study for each outcome. Omega-3 plus conventional therapy versus conventional therapy alone (two RCTs) For omega-3 plus conventional therapy versus conventional therapy alone, we found low certainty evidence suggesting an intergroup difference in symptoms favoring the omega-3 group (two studies, 70 participants; MD -7.16, 95% CI -13.97 to -0.34 OSDI units). Data could not be combined for all other outcomes. Long-chain omega-3 (EPA and DHA) versus omega-6 (five RCTs) For long-chain omega-3 versus omega-6 supplementation, we found moderate certainty evidence for a probable improvement in dry eye symptoms (two studies, 130 participants; MD -11.88, 95% CI -18.85 to -4.92 OSDI units). Meta-analysis was not possible for outcomes relating to ocular surface staining, Schirmer test or TBUT. We found low certainty evidence for a potential improvement in tear osmolarity (one study, 105 participants; MD -11.10, 95% CI -12.15 to -10.05 mOsmol/L). There was low level certainty regarding any potential effect on gastrointestinal side effects (two studies, 91 participants; RR 2.34, 95% CI 0.35 to 15.54).
AUTHORS' CONCLUSIONS
Overall, the findings in this review suggest a possible role for long-chain omega-3 supplementation in managing dry eye disease, although the evidence is uncertain and inconsistent. A core outcome set would work toward improving the consistency of reporting and the capacity to synthesize evidence.
Topics: Dry Eye Syndromes; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Humans; Lubricant Eye Drops; Ophthalmic Solutions; Randomized Controlled Trials as Topic
PubMed: 31847055
DOI: 10.1002/14651858.CD011016.pub2 -
Respiratory Care Jan 2020ARDS is an overwhelming systemic inflammatory process associated with significant morbidity and mortality. Several trials have evaluated the effects of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
ARDS is an overwhelming systemic inflammatory process associated with significant morbidity and mortality. Several trials have evaluated the effects of pharmaconutrients, given as part of a feeding formula or as a nutritional supplement, on clinical outcomes in critical illness and ARDS. The aim of this review is to assess the effects of immunonutrition on mechanically ventilated adults with ARDS compared to the standard feeding formula.
METHODS
We searched MEDLINE, EMBASE, CENTRAL, conference proceedings, and trial registries for appropriate studies up to April 2018. We performed statistical analysis according to Cochrane methodological standards. We used the GRADE approach to assess the quality of evidence for each outcome.
RESULTS
We identified 10 randomized controlled trials with 1,015 participants. All of the studies compared an enteral formula or additional supplemental omega-3 fatty acids (eg, eicosapentaenoic acid, docosahexaenoic acid), γ-linolenic acid, and antioxidants. All of the studies reported mortality. For the primary outcome, there was no difference in all-cause mortality (for the longest period reported) with the use of an immunonutrition enteral formula or additional supplements of omega-3 fatty acids, γ-linolenic acid, and antioxidants (risk ratio = 0.79, 95% CI 0.59-1.07; low-quality evidence). For the secondary outcomes, we are uncertain whether immunonutrition with omega-3 fatty acids and antioxidants improves ICU length of stay, ventilator days, and oxygenation or increases harm.
CONCLUSIONS
This Cochrane meta-analysis of 10 studies of varying quality examined the effects of omega-3 fatty acids and antioxidants in adults with ARDS. This intervention may produce little or no difference in all-cause mortality between groups. We are uncertain whether immunonutrition with omega-3 fatty acids and antioxidants improves ventilator days, ICU length of stay, or oxygenation due to the very low quality of evidence.
Topics: Antioxidants; Cause of Death; Dietary Supplements; Docosahexaenoic Acids; Eicosapentaenoic Acid; Enteral Nutrition; Fatty Acids, Omega-3; Humans; Randomized Controlled Trials as Topic; Respiration, Artificial; Respiratory Distress Syndrome; gamma-Linolenic Acid
PubMed: 31506339
DOI: 10.4187/respcare.06965 -
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 -
The Cochrane Database of Systematic... Jun 2019Conventionally used soybean oil-based lipid emulsion (S-LE) have high polyunsaturated fatty acid (PUFA) content and phytosterols that may contribute to adverse effects... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Conventionally used soybean oil-based lipid emulsion (S-LE) have high polyunsaturated fatty acid (PUFA) content and phytosterols that may contribute to adverse effects in preterm infants. The newer lipid emulsions (LE) from different lipid sources are currently available for use in preterm infants.
OBJECTIVES
To compare the safety and efficacy of all LE for parenteral nutrition (PN) in preterm infants (less than 37 weeks' gestation) including preterm infants with surgical conditions or parenteral nutrition-associated liver disease (PNALD)/cholestasis using direct comparisons and pair-wise meta-analyses.
SEARCH METHODS
We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 5), MEDLINE (1946 to 18 June 2018), Embase (1974 to 18 July 2018), CINAHL (1982 to 18 June 2018), MIDRIS (1971 to 31 May 2018), conference proceedings, trial registries (ClinicalTrials.gov and WHO's Trials Registry and Platform), and reference lists of retrieved articles.
SELECTION CRITERIA
Randomised or quasi-randomised controlled studies in preterm infants with or without surgical conditions or PNALD within the first six months of life.
DATA COLLECTION AND ANALYSIS
Data collection and analysis conformed to the methods of Cochrane Neonatal. We used the GRADE approach to assess the quality of evidence for important outcomes in addition to reporting statistical significance of results.
MAIN RESULTS
We included 29 studies (n = 2037) in this review. LE were classified in three broad groups: 1. all fish oil-containing LE including pure fish oil-LE (F-LE) and multisource LE (e.g. medium-chain triglycerides (MCT)-olive-fish-soybean oil-LE (MOFS-LE), MCT-fish-soybean oil-LE (MFS-LE) and olive-fish-soybean oil-LE (OFS-LE); 2. conventional S-LE; 3. alternative-LE (e.g. MCT-soybean oil-LE (MS-LE), olive-soybean oil-LE and borage oil-based LE).We considered the following broad comparisons: fish oil LE versus non-fish oil LE; fish oil LE versus another fish oil LE; alternative-LE versus S-LE; alternative-LE versus another alternative-LE in preterm infants less than 37 weeks' gestation, preterm infants with surgical conditions and preterm infants with PNALD/cholestasis. Separate subgroup comparisons of each LE preparation were included within these broader groups.Most studies in preterm infants used PN for mean duration of four weeks or less and for longer duration in infants with cholestasis or surgical conditions.We defined the primary outcome of PNALD/cholestasis as conjugated bilirubin (Cbil) 2 mg/dL or greater and resolution of PNALD/cholestasis as Cbil less than 2 mg/dL. There was heterogeneity in definitions used by the included studies with Cbil cut-offs ranging from 17.1 μmol/L (1 mg/dL) up to 50 μmol/L (about 3 mg/dL).In preterm infants, meta-analysis found no evidence of a difference in the incidence of PNALD/cholestasis (Cbil cut-off: 2 mg/dl) between fish oil-LEs and all non-fish oil LEs (typical risk ratio (RR) 0.61, 95% confidence interval (CI) 0.24 to 1.56; typical risk difference (RD) -0.03, 95% CI -0.08 to 0.02; 4 studies; n = 328; low-quality evidence).We also considered an outcome allowing for any definition of PNALD (different Cbil cutoffs). In the meta-analysis for PNALD/cholestasis, using any definition and restricted to low or unclear risk of bias studies, there was no evidence of a difference between fish oil LE and all non-fish oil LE for incidence of cholestasis (typical RR 0.80, 95% CI 0.53 to 1.21; typical RD -0.02, 95% CI -0.05 to 0.02; 10 studies; n = 1024; low-quality evidence). There was no evidence of difference in subgroup meta-analyses of individual LE types in any comparison.In preterm infants with surgical conditions or cholestasis, there was only one small study each reporting no evidence of a difference in incidence or resolution of cholestasis respectively with use of a pure F-LE versus S-LE (using a Cbil cut-off of 2 mg/dL).In preterm infants with PNALD/cholestasis (using any definition), the meta-analysis showed significantly less cholestasis with the use of fish oil-LE compared to S-LE (typical RR 0.54, 95% CI 0.32 to 0.91; typical RD -0.39, 95% CI -0.65 to -0.12; number needed to treat for an additional beneficial outcome (NNTB) 3, 95% CI 2 to 9; 2 studies; n = 40; very low-quality evidence). However, this outcome had a very low number of participants from two small studies with methodological differences, one of which was terminated early, increasing the uncertainty about effect estimates.There were no differences between LE types in pair-wise meta-analyses for growth in preterm infants. There was paucity of studies in preterm infants with surgical conditions or cholestasis to perform meta-analyses for growth and most other outcomes.In the secondary outcomes for preterm infants, there was no difference between fish-oil LE and non-fish oil LE in meta-analysis for severe retinopathy of prematurity (ROP) (stage 3 or greater, or requiring surgery: typical RR 0.80, 95% CI 0.55 to 1.16; typical RD -0.03, 95% CI -0.07 to 0.02; 7 studies; n = 731; very low-quality evidence). There were no differences in the LE types in pair-wise meta-analyses for death, bronchopulmonary dysplasia (BPD), ventilation duration, patent ductus arteriosus, sepsis, necrotising enterocolitis, intraventricular haemorrhage, periventricular leukomalacia, jaundice, hyperglycaemia, hypertriglyceridaemia, intrahepatocellular lipid content and conjugated bilirubin levels in any comparison.In surgical infants, one study (n = 19) reported no differences in death, sepsis rates, Cbil and neurodevelopmental outcomes with pure F-LE versus S-LE.In infants with cholestasis, there were no evidence of differences in death or sepsis in meta-analyses between fish oil-LE and S-LE; (2 studies; n = 40; very low-quality evidence).
AUTHORS' CONCLUSIONS
In the current review, we did not find any particular LE with or without fish oil to be better than another LE in preterm infants for prevention of PNALD/cholestasis, growth, mortality, ROP, BPD and other neonatal outcomes.In preterm infants with surgical conditions or cholestasis, there is currently insufficient evidence from randomised studies to determine with any certainty if fish oil LEs offer advantage in prevention or resolution of cholestasis or in any other clinical outcome.Further research, with larger well-designed trials, is warranted to evaluate the ideal composition of LE in preterm infants and the role of fish oil-containing and other LEs in the prevention and resolution of PNALD, ROP and other clinical outcomes.
Topics: Bilirubin; Bronchopulmonary Dysplasia; Chemical and Drug Induced Liver Injury; Cholestasis; Emulsions; Fish Oils; Humans; Infant, Newborn; Infant, Premature; Parenteral Nutrition; Plant Oils; Randomized Controlled Trials as Topic; Retinopathy of Prematurity; Soybean Oil; Surgical Procedures, Operative; gamma-Linolenic Acid
PubMed: 31158919
DOI: 10.1002/14651858.CD013163.pub2 -
The British Journal of Nutrition Jun 2019We conducted a systematic review of randomised controlled trials (RCT) of increased intake of arachidonic acid (ARA) on fatty acid status and health outcomes in humans....
We conducted a systematic review of randomised controlled trials (RCT) of increased intake of arachidonic acid (ARA) on fatty acid status and health outcomes in humans. We identified twenty-two articles from fourteen RCT. Most studies were conducted in adults. These used between 80 and 2000 mg ARA per d and were of 1-12 weeks duration. Supplementation with ARA doses as low as 80 mg/d increased the content of ARA in different blood fractions. Overall there seem to be few marked benefits for adults of increasing ARA intake from the typical usual intake of 100-200 mg/d to as much as 1000 mg/d; the few studies using higher doses (1500 or 2000 mg/d) also report little benefit. However, there may be an impact of ARA on cognitive and muscle function which could be particularly relevant in the ageing population. The studies reviewed here suggest no adverse effects in adults of increased ARA intake up to at least 1000-1500 mg/d on blood lipids, platelet aggregation and blood clotting, immune function, inflammation or urinary excretion of ARA metabolites. However, in many areas there are insufficient studies to make firm conclusions, and higher intakes of ARA are deserving of further study. Based on the RCT reviewed, there are not enough data to make any recommendations for specific health effects of ARA intake.
Topics: Adult; Aged; Arachidonic Acid; Dietary Supplements; Fatty Acids, Unsaturated; Female; Humans; Male; Middle Aged; Nutritional Status; Randomized Controlled Trials as Topic
PubMed: 31130146
DOI: 10.1017/S0007114519000692 -
BMJ Open May 2019To create a database of long-term randomised controlled trials (RCTs) comparing higher with lower omega-3, omega-6 or total polyunsaturated fatty acid (PUFA), regardless...
OBJECTIVE
To create a database of long-term randomised controlled trials (RCTs) comparing higher with lower omega-3, omega-6 or total polyunsaturated fatty acid (PUFA), regardless of reported outcomes, and to develop methods to assess effects of increasing omega-6, alpha-linolenic acid (ALA), long-chain omega-3 (LCn3) and total PUFA on health outcomes.
DESIGN
Systematic review search, methodology and meta-analyses.
DATA SOURCES
Medline, Embase, CENTRAL, WHO International Clinical Trials Registry Platform, Clinicaltrials.gov and trials in relevant systematic reviews.
ELIGIBILITY CRITERIA
RCTs of ≥24 weeks' duration assessing effects of increasing ALA, LCn3, omega-6 or total PUFAs, regardless of outcomes reported.
DATA SYNTHESIS
Methods included random-effects meta-analyses and sensitivity analyses. Funnel plots were examined, and subgrouping assessed effects of intervention type, replacement, baseline diabetes risk and use of diabetic medications, trial duration and dose. Quality of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE).
RESULTS
Electronic searches generated 37 810 hits, de-duplicated to 19 772 titles and abstracts. We assessed 2155 full-text papers, conference abstracts and trials registry entries independently in duplicate. Included studies were grouped into 363 RCTs comparing higher with lower omega-3, omega-6 and/or total PUFA intake of at least 6 months' duration-the Database.Of these 363 included RCTs, 216 RCTs were included in at least one of our reviews of health outcomes, data extracted and risk of bias assessed in duplicate. Ninety five RCTs were included in the Database but not included in our current reviews. Of these 311 completed trials, 27 altered ALA intake, 221 altered LCn3 intake and 16 trials altered omega-3 intake without specifying whether ALA or LCn3. Forty one trials altered omega-6 and 59 total PUFA.The remaining 52 trials are ongoing though 13 (25%) appear to be outstanding, or constitute missing data.
CONCLUSIONS
This extensive database of trials is available to allow assessment of further health outcomes.
Topics: Chronic Disease; Databases, Factual; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Health Behavior; Humans; Randomized Controlled Trials as Topic
PubMed: 31129605
DOI: 10.1136/bmjopen-2019-029554