Impact of home food production on nutritional blindness, stunting, wasting, underweight and mortality in children: a systematic review and meta-analysis of controlled trials.

Vitamin A deficiency is highly prevalent and remains the major cause of nutritional blindness in children in low-and middle-income countries, despite supplementation programmes. Xeropthalmia (severe drying and thickening of the conjunctiva) is caused by vitamin A deficiency and leads to irreversible blindness. Vitamin A supplementation programmes effectively reduce vitamin A deficiency but many rural children are not reached. Home food production may help prevent rural children's vitamin A deficiency. We aimed to systematically review trials assessing effects of home food production (also called homestead food production and agricultural interventions) on xeropthalmia, nightblindness, stunting, wasting, underweight and mortality (primary outcomes). We searched Medline, Embase, Scopus, Cochrane CENTRAL and trials registers to February 2019. Inclusion of studies, data extraction and risk of bias were assessed independently in duplicate. Random-effects meta-analysis, sensitivity analyses, subgrouping and GRADE were used. We included 16 trials randomizing 2498 children, none reported xerophthalmia, night-blindness or mortality. Home food production may slightly reduce stunting (mean difference (MD) 0.13 (z-score), 95% CI 0.01 to 0.24), wasting (MD 0.05 (z-score), 95% CI -0.04 to 0.14) and underweight (MD 0.07 (z-score), 95% CI -0.01 to 0.15) in young children (all GRADE low-consistency evidence), and increase dietary diversity (standardized mean difference (SMD) 0.24, 95% CI 0.15 to 0.34). Home food production may usefully complement vitamin A supplementation for rural children. Large, long-duration trials with good randomization, allocation concealment and correct adjustment for clustering are needed to assess effectiveness of home food production on nutritional blindness in young children.

Antibiotic prophylaxis for preventing bacterial endocarditis following dental procedures.

BACKGROUND: Infective endocarditis is a severe infection arising in the lining of the chambers of the heart. It can be caused by fungi, but most often is caused by bacteria. Many dental procedures cause bacteraemia, which could lead to bacterial endocarditis in a small proportion of people. The incidence of bacterial endocarditis is low, but it has a high mortality rate.  Guidelines in many countries have recommended that antibiotics be administered to people at high risk of endocarditis prior to invasive dental procedures. However, guidance by the National Institute for Health and Care Excellence (NICE) in England and Wales states that antibiotic prophylaxis against infective endocarditis is not recommended routinely for people undergoing dental procedures. This is an update of a review that we first conducted in 2004 and last updated in 2013. OBJECTIVES: Primary objective To determine whether prophylactic antibiotic administration, compared to no antibiotic administration or placebo, before invasive dental procedures in people at risk or at high risk of bacterial endocarditis, influences mortality, serious illness or the incidence of endocarditis. Secondary objectives To determine whether the effect of dental antibiotic prophylaxis differs in people with different cardiac conditions predisposing them to increased risk of endocarditis, and in people undergoing different high risk dental procedures. Harms Had we foundno evidence from randomised controlled trials or cohort studies on whether prophylactic antibiotics affected mortality or serious illness, and we had found evidence from these or case-control studies suggesting that prophylaxis with antibiotics reduced the incidence of endocarditis, then we would also have assessed whether the harms of prophylaxis with single antibiotic doses, such as with penicillin (amoxicillin 2 g or 3 g) before invasive dental procedures, compared with no antibiotic or placebo, equalled the benefits in prevention of endocarditis in people at high risk of this disease. SEARCH METHODS: An information specialist searched four bibliographic databases up to 10 May 2021 and used additional search methods to identify published, unpublished and ongoing studies SELECTION CRITERIA: Due to the low incidence of bacterial endocarditis, we anticipated that few if any trials would be located. For this reason, we included cohort and case-control studies with suitably matched control or comparison groups. The intervention was antibiotic prophylaxis, compared to no antibiotic prophylaxis or placebo, before a dental procedure in people with an increased risk of bacterial endocarditis. Cohort studies would need to follow at-risk individuals and assess outcomes following any invasive dental procedures, grouping participants according to whether or not they had received prophylaxis. Case-control studies would need to match people who had developed endocarditis after undergoing an invasive dental procedure (and who were known to be at increased risk before undergoing the procedure) with those at similar risk who had not developed endocarditis.  Our outcomes of interest were mortality or serious adverse events requiring hospital admission; development of endocarditis following any dental procedure in a defined time period; development of endocarditis due to other non-dental causes; any recorded adverse effects of the antibiotics; and the cost of antibiotic provision compared to that of caring for patients who developed endocarditis. DATA COLLECTION AND ANALYSIS: Two review authors independently screened search records, selected studies for inclusion, assessed the risk of bias in the included study and extracted data from the included study. As an author team, we judged the certainty of the evidence identified for the main comparison and key outcomes using GRADE criteria. We presented the main results in a summary of findings table. MAIN RESULTS: Our new search did not find any new studies for inclusion since the last version of the review in 2013. No randomised controlled trials (RCTs), controlled clinical trials (CCTs) or cohort studies were included in the previous versions of the review, but one case-control study met the inclusion criteria. The trial authors collected information on 48 people who had contracted bacterial endocarditis over a specific two-year period and had undergone a medical or dental procedure with an indication for prophylaxis within the past 180 days. These people were matched to a similar group of people who had not contracted bacterial endocarditis. All study participants had undergone an invasive medical or dental procedure. The two groups were compared to establish whether those who had received preventive antibiotics (penicillin) were less likely to have developed endocarditis. The authors found no significant effect of penicillin prophylaxis on the incidence of endocarditis. No data on other outcomes were reported. The level of certainty we have about the evidence is very low. AUTHORS' CONCLUSIONS: There remains no clear evidence about whether antibiotic prophylaxis is effective or ineffective against bacterial endocarditis in at-risk people who are about to undergo an invasive dental procedure. We cannot determine whether the potential harms and costs of antibiotic administration outweigh any beneficial effect. Ethically, practitioners should discuss the potential benefits and harms of antibiotic prophylaxis with their patients before a decision is made about administration.

Omega-3 and polyunsaturated fat for prevention of depression and anxiety symptoms: systematic review and meta-analysis of randomised trials.

BACKGROUND: There is strong public belief that polyunsaturated fats protect against and ameliorate depression and anxiety. AIMS: To assess effects of increasing omega-3, omega-6 or total polyunsaturated fat on prevention and treatment of depression and anxiety symptoms. METHOD: We searched widely (Central, Medline and EMBASE to April 2017, trial registers to September 2016, ongoing trials updated to August 2019), including trials of adults with or without depression or anxiety, randomised to increased omega-3, omega-6 or total polyunsaturated fat for ≥24 weeks, excluding multifactorial interventions. Inclusion, data extraction and risk of bias were assessed independently in duplicate, and authors contacted for further data. We used random-effects meta-analysis, sensitivity analyses, subgrouping and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) assessment. RESULTS: We included 31 trials assessing effects of long-chain omega-3 (n = 41 470), one of alpha-linolenic acid (n = 4837), one of total polyunsaturated fat (n = 4997) and none of omega-6. Meta-analysis suggested that increasing long-chain omega-3 probably has little or no effect on risk of depression symptoms (risk ratio 1.01, 95% CI 0.92-1.10, I2 = 0%, median dose 0.95 g/d, duration 12 months) or anxiety symptoms (standardised mean difference 0.15, 95% CI 0.05-0.26, I2 = 0%, median dose 1.1 g/d, duration 6 months; both moderate-quality evidence). Evidence of effects on depression severity and remission in existing depression were unclear (very-low-quality evidence). Results did not differ by risk of bias, omega-3 dose, duration or nutrients replaced. Increasing alpha-linolenic acid by 2 g/d may increase risk of depression symptoms very slightly over 40 months (number needed to harm, 1000). CONCLUSIONS: Long-chain omega-3 supplementation probably has little or no effect in preventing depression or anxiety symptoms. DECLARATION OF INTEREST: L.H. and A.A. were funded to attend the World Health Organization Nutrition Guidance Expert Advisory Group (NUGAG) Subgroup on Diet and Health meetings and present review results. The authors report no other conflicts of interest.

Long-term effects of increasing omega-3, omega-6 and total polyunsaturated fats on inflammatory bowel disease and markers of inflammation: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: Effects of long-chain omega-3 (LCn3) and omega-6 fatty acids on prevention and treatment of inflammatory bowel diseases (IBD, including Crohn's Disease, CD and ulcerative colitis, UC), and inflammation are unclear. We systematically reviewed long-term effects of omega-3, omega-6 and total polyunsaturated fats (PUFA) on IBD diagnosis, relapse, severity, pharmacotherapy, quality of life and key inflammatory markers. METHODS: We searched Medline, Embase, Cochrane CENTRAL, and trials registries, including RCTs in adults with or without IBD comparing higher with lower omega-3, omega-6 and/or total PUFA intake for ≥ 24 weeks that assessed IBD-specific outcomes or inflammatory biomarkers. RESULTS: We included 83 RCTs (41,751 participants), of which 13 recruited participants with IBD. Increasing LCn3 may reduce risk of IBD relapse (RR 0.85, 95% CI 0.72-1.01) and IBD worsening (RR 0.85, 95% CI 0.71-1.03), and reduce erythrocyte sedimentation rate (ESR, SMD - 0.23, 95% CI - 0.44 to - 0.01), but may increase IBD diagnosis risk (RR 1.10, 95% CI 0.63-1.92), and faecal calprotectin, a specific inflammatory marker for IBD (MD 16.1 µg/g, 95% CI - 37.6 to 69.8, all low-quality evidence). Outcomes for alpha-linolenic acid, omega-6 and total PUFA were sparse, but suggested little or no effect where data were available. CONCLUSION: This is the most comprehensive meta-analysis of RCTs investigating long-term effects of omega-3, omega-6 and total PUFA on IBD and inflammatory markers. Our findings suggest that supplementation with PUFAs has little or no effect on prevention or treatment of IBD and provides little support for modification of long-term inflammatory status.

Omega-3, omega-6 and total dietary polyunsaturated fat on cancer incidence: systematic review and meta-analysis of randomised trials.

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.

Reduction in saturated fat intake for cardiovascular disease.

BACKGROUND: Reducing saturated fat reduces serum cholesterol, but effects on other intermediate outcomes may be less clear. Additionally, it is unclear whether the energy from saturated fats eliminated from the diet are more helpfully replaced by polyunsaturated fats, monounsaturated fats, carbohydrate or protein. OBJECTIVES: To assess the effect of reducing saturated fat intake and replacing it with carbohydrate (CHO), polyunsaturated (PUFA), monounsaturated fat (MUFA) and/or protein on mortality and cardiovascular morbidity, using all available randomised clinical trials. SEARCH METHODS: We updated our searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid) and Embase (Ovid) on 15 October 2019, and searched Clinicaltrials.gov and WHO International Clinical Trials Registry Platform (ICTRP) on 17 October 2019. SELECTION CRITERIA: Included trials fulfilled the following criteria: 1) randomised; 2) intention to reduce saturated fat intake OR intention to alter dietary fats and achieving a reduction in saturated fat; 3) compared with higher saturated fat intake or usual diet; 4) not multifactorial; 5) in adult humans with or without cardiovascular disease (but not acutely ill, pregnant or breastfeeding); 6) intervention duration at least 24 months; 7) mortality or cardiovascular morbidity data available. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed inclusion, extracted study data and assessed risk of bias. We performed random-effects meta-analyses, meta-regression, subgrouping, sensitivity analyses, funnel plots and GRADE assessment. MAIN RESULTS: We included 15 randomised controlled trials (RCTs) (16 comparisons, 56,675 participants), that used a variety of interventions from providing all food to advice on reducing saturated fat. The included long-term trials suggested that reducing dietary saturated fat reduced the risk of combined cardiovascular events by 17% (risk ratio (RR) 0.83; 95% confidence interval (CI) 0.70 to 0.98, 12 trials, 53,758 participants of whom 8% had a cardiovascular event, I² = 67%, GRADE moderate-quality evidence). Meta-regression suggested that greater reductions in saturated fat (reflected in greater reductions in serum cholesterol) resulted in greater reductions in risk of CVD events, explaining most heterogeneity between trials. The number needed to treat for an additional beneficial outcome (NNTB) was 56 in primary prevention trials, so 56 people need to reduce their saturated fat intake for ~four years for one person to avoid experiencing a CVD event. In secondary prevention trials, the NNTB was 53. Subgrouping did not suggest significant differences between replacement of saturated fat calories with polyunsaturated fat or carbohydrate, and data on replacement with monounsaturated fat and protein was very limited. We found little or no effect of reducing saturated fat on all-cause mortality (RR 0.96; 95% CI 0.90 to 1.03; 11 trials, 55,858 participants) or cardiovascular mortality (RR 0.95; 95% CI 0.80 to 1.12, 10 trials, 53,421 participants), both with GRADE moderate-quality evidence. There was little or no effect of reducing saturated fats on non-fatal myocardial infarction (RR 0.97, 95% CI 0.87 to 1.07) or CHD mortality (RR 0.97, 95% CI 0.82 to 1.16, both low-quality evidence), but effects on total (fatal or non-fatal) myocardial infarction, stroke and CHD events (fatal or non-fatal) were all unclear as the evidence was of very low quality. There was little or no effect on cancer mortality, cancer diagnoses, diabetes diagnosis, HDL cholesterol, serum triglycerides or blood pressure, and small reductions in weight, serum total cholesterol, LDL cholesterol and BMI. There was no evidence of harmful effects of reducing saturated fat intakes. AUTHORS' CONCLUSIONS: The findings of this updated review suggest that reducing saturated fat intake for at least two years causes a potentially important reduction in combined cardiovascular events. Replacing the energy from saturated fat with polyunsaturated fat or carbohydrate appear to be useful strategies, while effects of replacement with monounsaturated fat are unclear. The reduction in combined cardiovascular events resulting from reducing saturated fat did not alter by study duration, sex or baseline level of cardiovascular risk, but greater reduction in saturated fat caused greater reductions in cardiovascular events.

Reduction in saturated fat intake for cardiovascular disease.

BACKGROUND: Reducing saturated fat reduces serum cholesterol, but effects on other intermediate outcomes may be less clear. Additionally, it is unclear whether the energy from saturated fats eliminated from the diet are more helpfully replaced by polyunsaturated fats, monounsaturated fats, carbohydrate or protein. OBJECTIVES: To assess the effect of reducing saturated fat intake and replacing it with carbohydrate (CHO), polyunsaturated (PUFA), monounsaturated fat (MUFA) and/or protein on mortality and cardiovascular morbidity, using all available randomised clinical trials. SEARCH METHODS: We updated our searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid) and Embase (Ovid) on 15 October 2019, and searched Clinicaltrials.gov and WHO International Clinical Trials Registry Platform (ICTRP) on 17 October 2019. SELECTION CRITERIA: Included trials fulfilled the following criteria: 1) randomised; 2) intention to reduce saturated fat intake OR intention to alter dietary fats and achieving a reduction in saturated fat; 3) compared with higher saturated fat intake or usual diet; 4) not multifactorial; 5) in adult humans with or without cardiovascular disease (but not acutely ill, pregnant or breastfeeding); 6) intervention duration at least 24 months; 7) mortality or cardiovascular morbidity data available. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed inclusion, extracted study data and assessed risk of bias. We performed random-effects meta-analyses, meta-regression, subgrouping, sensitivity analyses, funnel plots and GRADE assessment. MAIN RESULTS: We included 15 randomised controlled trials (RCTs) (16 comparisons, ~59,000 participants), that used a variety of interventions from providing all food to advice on reducing saturated fat. The included long-term trials suggested that reducing dietary saturated fat reduced the risk of combined cardiovascular events by 21% (risk ratio (RR) 0.79; 95% confidence interval (CI) 0.66 to 0.93, 11 trials, 53,300 participants of whom 8% had a cardiovascular event, I² = 65%, GRADE moderate-quality evidence). Meta-regression suggested that greater reductions in saturated fat (reflected in greater reductions in serum cholesterol) resulted in greater reductions in risk of CVD events, explaining most heterogeneity between trials. The number needed to treat for an additional beneficial outcome (NNTB) was 56 in primary prevention trials, so 56 people need to reduce their saturated fat intake for ~four years for one person to avoid experiencing a CVD event. In secondary prevention trials, the NNTB was 32. Subgrouping did not suggest significant differences between replacement of saturated fat calories with polyunsaturated fat or carbohydrate, and data on replacement with monounsaturated fat and protein was very limited. We found little or no effect of reducing saturated fat on all-cause mortality (RR 0.96; 95% CI 0.90 to 1.03; 11 trials, 55,858 participants) or cardiovascular mortality (RR 0.95; 95% CI 0.80 to 1.12, 10 trials, 53,421 participants), both with GRADE moderate-quality evidence. There was little or no effect of reducing saturated fats on non-fatal myocardial infarction (RR 0.97, 95% CI 0.87 to 1.07) or CHD mortality (RR 0.97, 95% CI 0.82 to 1.16, both low-quality evidence), but effects on total (fatal or non-fatal) myocardial infarction, stroke and CHD events (fatal or non-fatal) were all unclear as the evidence was of very low quality. There was little or no effect on cancer mortality, cancer diagnoses, diabetes diagnosis, HDL cholesterol, serum triglycerides or blood pressure, and small reductions in weight, serum total cholesterol, LDL cholesterol and BMI. There was no evidence of harmful effects of reducing saturated fat intakes. AUTHORS' CONCLUSIONS: The findings of this updated review suggest that reducing saturated fat intake for at least two years causes a potentially important reduction in combined cardiovascular events. Replacing the energy from saturated fat with polyunsaturated fat or carbohydrate appear to be useful strategies, while effects of replacement with monounsaturated fat are unclear. The reduction in combined cardiovascular events resulting from reducing saturated fat did not alter by study duration, sex or baseline level of cardiovascular risk, but greater reduction in saturated fat caused greater reductions in cardiovascular events.

Effects of total fat intake on body fatness in adults.

BACKGROUND: The ideal proportion of energy from fat in our food and its relation to body weight is not clear. In order to prevent overweight and obesity in the general population, we need to understand the relationship between the proportion of energy from fat and resulting weight and body fatness in the general population. OBJECTIVES: To assess the effects of proportion of energy intake from fat on measures of body fatness (including body weight, waist circumference, percentage body fat and body mass index) in people not aiming to lose weight, using all appropriate randomised controlled trials (RCTs) of at least six months duration. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Clinicaltrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) to October 2019. We did not limit the search by language. SELECTION CRITERIA: Trials fulfilled the following criteria: 1) randomised intervention trial, 2) included adults aged at least 18 years, 3) randomised to a lower fat versus higher fat diet, without the intention to reduce weight in any participants, 4) not multifactorial and 5) assessed a measure of weight or body fatness after at least six months. We duplicated inclusion decisions and resolved disagreement by discussion or referral to a third party. DATA COLLECTION AND ANALYSIS: We extracted data on the population, intervention, control and outcome measures in duplicate. We extracted measures of body fatness (body weight, BMI, percentage body fat and waist circumference) independently in duplicate at all available time points. We performed random-effects meta-analyses, meta-regression, subgrouping, sensitivity, funnel plot analyses and GRADE assessment. MAIN RESULTS: We included 37 RCTs (57,079 participants). There is consistent high-quality evidence from RCTs that reducing total fat intake results in small reductions in body fatness; this was seen in almost all included studies and was highly resistant to sensitivity analyses (GRADE high-consistency evidence, not downgraded). The effect of eating less fat (compared with higher fat intake) is a mean body weight reduction of 1.4 kg (95% confidence interval (CI) -1.7 to -1.1 kg, in 53,875 participants from 26 RCTs, I2 = 75%). The heterogeneity was explained in subgrouping and meta-regression. These suggested that greater weight loss results from greater fat reductions in people with lower fat intake at baseline, and people with higher body mass index (BMI) at baseline. The size of the effect on weight does not alter over time and is mirrored by reductions in BMI (MD -0.5 kg/m2, 95% CI -0.6 to -0.3, 46,539 participants in 14 trials, I2 = 21%), waist circumference (MD -0.5 cm, 95% CI -0.7 to -0.2, 16,620 participants in 3 trials; I2 = 21%), and percentage body fat (MD -0.3% body fat, 95% CI -0.6 to 0.00, P = 0.05, in 2350 participants in 2 trials; I2 = 0%). There was no suggestion of harms associated with low fat diets that might mitigate any benefits on body fatness. The reduction in body weight was reflected in small reductions in LDL (-0.13 mmol/L, 95% CI -0.21 to -0.05), and total cholesterol (-0.23 mmol/L, 95% CI -0.32 to -0.14), with little or no effect on HDL cholesterol (-0.02 mmol/L, 95% CI -0.03 to 0.00), triglycerides (0.01 mmol/L, 95% CI -0.05 to 0.07), systolic (-0.75 mmHg, 95% CI -1.42 to -0.07) or diastolic blood pressure(-0.52 mmHg, 95% CI -0.95 to -0.09), all GRADE high-consistency evidence or quality of life (0.04, 95% CI 0.01 to 0.07, on a scale of 0 to 10, GRADE low-consistency evidence). AUTHORS' CONCLUSIONS: Trials where participants were randomised to a lower fat intake versus a higher fat intake, but with no intention to reduce weight, showed a consistent, stable but small effect of low fat intake on body fatness: slightly lower weight, BMI, waist circumference and percentage body fat compared with higher fat arms. Greater fat reduction, lower baseline fat intake and higher baseline BMI were all associated with greater reductions in weight. There was no evidence of harm to serum lipids, blood pressure or quality of life, but rather of small benefits or no effect.

Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease.

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.

Systematic review of modifiable risk factors shows little evidential support for most current practices in Cryptosporidium management in bovine calves.

Cryptosporidiosis is common in young calves, causing diarrhoea, delayed growth, poor condition and excess mortality. No vaccine or cure exists, although symptomatic onset may be delayed with some chemoprophylactics. Other response and management strategies have focused on nutritional status, cleanliness and biosecurity. We undertook a systematic review of observational studies to identify risk or protective factors that could prevent Cryptosporidium parvum infection in calves. Included studies used multivariate analysis within cohort, cross-sectional or case-control designs, of risk factors among young calves, assessing C. parvum specifically. We tabulated data on characteristics and study quality and present narrative synthesis. Fourteen eligible studies were found; three of which were higher quality. The most consistent evidence suggested that risk of C. parvum infection increased when calves had more contact with other calves, were in larger herds or in organic production. Hard flooring reduced risk of infection and calves tended to have more cryptosporidiosis during warm and wet weather. While many other factors were not found to be associated with C. parvum infection, analyses were usually badly underpowered, due to clustering of management factors. Trials are needed to assess effects of manipulating calf contact, herd size, organic methods, hard flooring and temperature. Other factors need to be assessed in larger observational studies with improved disaggregation of potential risk factors.

Community use of face masks and similar barriers to prevent respiratory illness such as COVID-19: a rapid scoping review.

BackgroundEvidence for face-mask wearing in the community to protect against respiratory disease is unclear.AimTo assess effectiveness of wearing face masks in the community to prevent respiratory disease, and recommend improvements to this evidence base.MethodsWe systematically searched Scopus, Embase and MEDLINE for studies evaluating respiratory disease incidence after face-mask wearing (or not). Narrative synthesis and random-effects meta-analysis of attack rates for primary and secondary prevention were performed, subgrouped by design, setting, face barrier type, and who wore the mask. Preferred outcome was influenza-like illness. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) quality assessment was undertaken and evidence base deficits described.Results33 studies (12 randomised control trials (RCTs)) were included. Mask wearing reduced primary infection by 6% (odds ratio (OR): 0.94; 95% CI: 0.75-1.19 for RCTs) to 61% (OR: 0.85; 95% CI: 0.32-2.27; OR: 0.39; 95% CI: 0.18-0.84 and OR: 0.61; 95% CI: 0.45-0.85 for cohort, case-control and cross-sectional studies respectively). RCTs suggested lowest secondary attack rates when both well and ill household members wore masks (OR: 0.81; 95% CI: 0.48-1.37). While RCTs might underestimate effects due to poor compliance and controls wearing masks, observational studies likely overestimate effects, as mask wearing might be associated with other risk-averse behaviours. GRADE was low or very low quality.ConclusionWearing face masks may reduce primary respiratory infection risk, probably by 6-15%. It is important to balance evidence from RCTs and observational studies when their conclusions widely differ and both are at risk of significant bias. COVID-19-specific studies are required.

The Relationship Between Omega-3, Omega-6 and Total Polyunsaturated Fat and Musculoskeletal Health and Functional Status in Adults: A Systematic Review and Meta-analysis of RCTs.

We conducted a systematic review and meta-analysis to assess the effects of increasing dietary omega-3, omega-6 and mixed polyunsaturated fatty acids (PUFA) on musculoskeletal health, functional status, sarcopenia and risk of fractures. We searched Medline, Embase, The Cochrane library, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) databases for Randomised Controlled Trials (RCTs) of adults evaluating the effects of higher versus lower oral omega-3, omega-6 or mixed PUFA for ≥ 6 months on musculoskeletal and functional outcomes. We included 28 RCTs (7288 participants, 31 comparisons), 23 reported effects of omega-3, one of omega-6 and four of mixed total PUFA. Participants and doses were heterogeneous. Six omega-3 trials were judged at low summary risk of bias. We found low-quality evidence that increasing omega-3 increased lumbar spine BMD by 2.6% (0.03 g/cm2, 95% CI - 0.02 to 0.07, 463 participants). There was also the suggestion of an increase in femoral neck BMD (of 4.1%), but the evidence was of very low quality. There may be little or no effect of omega-3 on functional outcomes and bone mass; effects on other outcomes were unclear. Only one study reported on effects of omega-6 with very limited data. Increasing total PUFA had little or no effect on BMD or indices of fat-free (skeletal) muscle mass (low-quality evidence); no data were available on fractures, BMD or functional status and data on bone turnover markers were limited. Trials assessing effects of increasing omega-3, omega-6 and total PUFA on functional status, bone and skeletal muscle strength are limited with data lacking or of low quality. Whilst there is an indication that omega-3 may improve BMD, high-quality RCTs are needed to confirm this and effects on other musculoskeletal outcomes.

WITHDRAWN: Ozone therapy for the treatment of dental caries.

BACKGROUND: Dental caries is a bacterially mediated disease characterised by demineralisation of the tooth surface, which may lead to cavitation, discomfort, pain and eventual tooth loss. Ozone is toxic to certain bacteria in vitro and it has been suggested that delivering ozone into a carious lesion might reduce the number of cariogenic bacteria. This possibly could arrest the progress of the lesion and may, in the presence of fluoride, perhaps allow remineralisation to occur. This may in turn delay or prevent the need for traditional dental conservation by 'drilling and filling'. OBJECTIVES: To assess whether ozone is effective in arresting or reversing the progression of dental caries. SEARCH METHODS: We searched the Cochrane Oral Health Group's Trials Register (to 7 November 2003); Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2003, Issue 3); MEDLINE and PREMEDLINE (OVID) (1966 to November 2003); EMBASE (OVID) (1980 to November 2003); CINAHL (OVID) (1982 to November 2003); AMED (OVID) (1985 to November 2003). Quintessence was handsearched through 2002 and KaVo were contacted as manufacturers of the HealOzone apparatus for any additional published or unpublished trials. SELECTION CRITERIA: Inclusion was assessed independently by at least two reviewers. Trials were only included if they met the following criteria: randomisation in a controlled trial; single surface in vivo carious lesion accessible to ozone application; clear allocation concealment; ozone application to the lesions in the intervention group; no such application of ozone in the control group; outcomes measured after at least 6 months. DATA COLLECTION AND ANALYSIS: Reviewers independently extracted information in duplicate. A paucity of comparable data did not allow meta-analytic pooling of the included studies. MAIN RESULTS: Three trials were included, with a combined total of 432 randomised lesions (137 participants). Forty-two conference papers, abstracts and posters were excluded (from an unknown number of studies). The risk of bias in all studies appeared high. The analyses of all three studies were conducted at the level of the lesion, which is not independent of the person, for this reason pooling of data was not appropriate or attempted. Individual studies showed inconsistent effects of ozone on caries, across different measures of caries progression or regression. Few secondary outcomes were reported, but one trial reported an absence of adverse events. AUTHORS' CONCLUSIONS: Given the high risk of bias in the available studies and lack of consistency between different outcome measures, there is no reliable evidence that application of ozone gas to the surface of decayed teeth stops or reverses the decay process. There is a fundamental need for more evidence of appropriate rigour and quality before the use of ozone can be accepted into mainstream primary dental care or can be considered a viable alternative to current methods for the management and treatment of dental caries.

Interventions for preventing obesity in children.

BACKGROUND: Prevention of childhood obesity is an international public health priority given the significant impact of obesity on acute and chronic diseases, general health, development and well-being. The international evidence base for strategies to prevent obesity is very large and is accumulating rapidly. This is an update of a previous review. OBJECTIVES: To determine the effectiveness of a range of interventions that include diet or physical activity components, or both, designed to prevent obesity in children. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, PsychINFO and CINAHL in June 2015. We re-ran the search from June 2015 to January 2018 and included a search of trial registers. SELECTION CRITERIA: Randomised controlled trials (RCTs) of diet or physical activity interventions, or combined diet and physical activity interventions, for preventing overweight or obesity in children (0-17 years) that reported outcomes at a minimum of 12 weeks from baseline. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data, assessed risk-of-bias and evaluated overall certainty of the evidence using GRADE. We extracted data on adiposity outcomes, sociodemographic characteristics, adverse events, intervention process and costs. We meta-analysed data as guided by the Cochrane Handbook for Systematic Reviews of Interventions and presented separate meta-analyses by age group for child 0 to 5 years, 6 to 12 years, and 13 to 18 years for zBMI and BMI. MAIN RESULTS: We included 153 RCTs, mostly from the USA or Europe. Thirteen studies were based in upper-middle-income countries (UMIC: Brazil, Ecuador, Lebanon, Mexico, Thailand, Turkey, US-Mexico border), and one was based in a lower middle-income country (LMIC: Egypt). The majority (85) targeted children aged 6 to 12 years.Children aged 0-5 years: There is moderate-certainty evidence from 16 RCTs (n = 6261) that diet combined with physical activity interventions, compared with control, reduced BMI (mean difference (MD) -0.07 kg/m2, 95% confidence interval (CI) -0.14 to -0.01), and had a similar effect (11 RCTs, n = 5536) on zBMI (MD -0.11, 95% CI -0.21 to 0.01). Neither diet (moderate-certainty evidence) nor physical activity interventions alone (high-certainty evidence) compared with control reduced BMI (physical activity alone: MD -0.22 kg/m2, 95% CI -0.44 to 0.01) or zBMI (diet alone: MD -0.14, 95% CI -0.32 to 0.04; physical activity alone: MD 0.01, 95% CI -0.10 to 0.13) in children aged 0-5 years.Children aged 6 to 12 years: There is moderate-certainty evidence from 14 RCTs (n = 16,410) that physical activity interventions, compared with control, reduced BMI (MD -0.10 kg/m2, 95% CI -0.14 to -0.05). However, there is moderate-certainty evidence that they had little or no effect on zBMI (MD -0.02, 95% CI -0.06 to 0.02). There is low-certainty evidence from 20 RCTs (n = 24,043) that diet combined with physical activity interventions, compared with control, reduced zBMI (MD -0.05 kg/m2, 95% CI -0.10 to -0.01). There is high-certainty evidence that diet interventions, compared with control, had little impact on zBMI (MD -0.03, 95% CI -0.06 to 0.01) or BMI (-0.02 kg/m2, 95% CI -0.11 to 0.06).Children aged 13 to 18 years: There is very low-certainty evidence that physical activity interventions, compared with control reduced BMI (MD -1.53 kg/m2, 95% CI -2.67 to -0.39; 4 RCTs; n = 720); and low-certainty evidence for a reduction in zBMI (MD -0.2, 95% CI -0.3 to -0.1; 1 RCT; n = 100). There is low-certainty evidence from eight RCTs (n = 16,583) that diet combined with physical activity interventions, compared with control, had no effect on BMI (MD -0.02 kg/m2, 95% CI -0.10 to 0.05); or zBMI (MD 0.01, 95% CI -0.05 to 0.07; 6 RCTs; n = 16,543). Evidence from two RCTs (low-certainty evidence; n = 294) found no effect of diet interventions on BMI.Direct comparisons of interventions: Two RCTs reported data directly comparing diet with either physical activity or diet combined with physical activity interventions for children aged 6 to 12 years and reported no differences.Heterogeneity was apparent in the results from all three age groups, which could not be entirely explained by setting or duration of the interventions. Where reported, interventions did not appear to result in adverse effects (16 RCTs) or increase health inequalities (gender: 30 RCTs; socioeconomic status: 18 RCTs), although relatively few studies examined these factors.Re-running the searches in January 2018 identified 315 records with potential relevance to this review, which will be synthesised in the next update. AUTHORS' CONCLUSIONS: Interventions that include diet combined with physical activity interventions can reduce the risk of obesity (zBMI and BMI) in young children aged 0 to 5 years. There is weaker evidence from a single study that dietary interventions may be beneficial.However, interventions that focus only on physical activity do not appear to be effective in children of this age. In contrast, interventions that only focus on physical activity can reduce the risk of obesity (BMI) in children aged 6 to 12 years, and adolescents aged 13 to 18 years. In these age groups, there is no evidence that interventions that only focus on diet are effective, and some evidence that diet combined with physical activity interventions may be effective. Importantly, this updated review also suggests that interventions to prevent childhood obesity do not appear to result in adverse effects or health inequalities.The review will not be updated in its current form. To manage the growth in RCTs of child obesity prevention interventions, in future, this review will be split into three separate reviews based on child age.

Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease.

BACKGROUND: Researchers have suggested that 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)) benefit cardiovascular health. Guidelines recommend increasing omega-3-rich foods, and sometimes supplementation, but recent trials have not confirmed this. OBJECTIVES: To assess effects of increased intake of fish- and plant-based omega-3 for all-cause mortality, cardiovascular (CVD) events, adiposity and lipids. SEARCH METHODS: We searched CENTRAL, MEDLINE and Embase to April 2017, plus ClinicalTrials.gov and World Health Organization International Clinical Trials Registry to September 2016, with no language restrictions. We handsearched systematic review references and bibliographies and contacted authors. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that lasted at least 12 months and compared supplementation and/or advice to increase LCn3 or ALA intake versus usual or lower intake. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies 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 79 RCTs (112,059 participants) in this review update and found that 25 were at low summary risk of bias. Trials were of 12 to 72 months' duration and included adults at varying cardiovascular risk, mainly in high-income countries. Most studies 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 0.5g/d LCn3 to > 5 g/d (16 RCTs gave at least 3g/d LCn3).Meta-analysis and sensitivity analyses suggested little or no effect of increasing LCn3 on all-cause mortality (RR 0.98, 95% CI 0.90 to 1.03, 92,653 participants; 8189 deaths in 39 trials, high-quality evidence), cardiovascular mortality (RR 0.95, 95% CI 0.87 to 1.03, 67,772 participants; 4544 CVD deaths in 25 RCTs), cardiovascular events (RR 0.99, 95% CI 0.94 to 1.04, 90,378 participants; 14,737 people experienced events in 38 trials, high-quality evidence), coronary heart disease (CHD) mortality (RR 0.93, 95% CI 0.79 to 1.09, 73,491 participants; 1596 CHD deaths in 21 RCTs), stroke (RR 1.06, 95% CI 0.96 to 1.16, 89,358 participants; 1822 strokes in 28 trials) or arrhythmia (RR 0.97, 95% CI 0.90 to 1.05, 53,796 participants; 3788 people experienced arrhythmia in 28 RCTs). There was a suggestion that LCn3 reduced CHD events (RR 0.93, 95% CI 0.88 to 0.97, 84,301 participants; 5469 people experienced CHD events in 28 RCTs); however, this was not maintained in sensitivity analyses - LCn3 probably makes little or no difference to CHD event risk. All evidence was of moderate GRADE quality, except as noted.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, 5 RCTs),cardiovascular mortality (RR 0.96, 95% CI 0.74 to 1.25, 18,619 participants; 219 cardiovascular deaths, 4 RCTs), and CHD mortality (1.1% to 1.0%, RR 0.95, 95% CI 0.72 to 1.26, 18,353 participants; 193 CHD deaths, 3 RCTs) and ALA may make little or no difference to CHD events (RR 1.00, 95% CI 0.80 to 1.22, 19,061 participants, 397 CHD events, 4 RCTs, low-quality evidence). However, increased ALA may slightly reduce risk of cardiovascular events (from 4.8% to 4.7%, RR 0.95, 95% CI 0.83 to 1.07, 19,327 participants; 884 CVD events, 5 RCTs, low-quality evidence with greater effects in trials at low summary risk of bias), and probably reduces risk of arrhythmia (3.3% to 2.6%, RR 0.79, 95% CI 0.57 to 1.10, 4,837 participants; 141 events, 1 RCT). Effects on stroke are unclear.Sensitivity analysis retaining only trials at low summary risk of bias moved effect sizes towards the null (RR 1.0) for all LCn3 primary outcomes except arrhythmias, but for most ALA outcomes, effect sizes moved to suggest protection. LCn3 funnel plots suggested that adding in missing studies/results would move effect sizes towards null for most primary outcomes. There were no dose or duration effects in subgrouping or meta-regression.There was no evidence that increasing LCn3 or ALA altered serious adverse events, adiposity or lipids, except LCn3 reduced triglycerides by ˜15% in a dose-dependant way (high-quality evidence). AUTHORS' CONCLUSIONS: This is the most extensive systematic assessment of effects of omega-3 fats on cardiovascular health to date. Moderate- and high-quality evidence suggests that increasing EPA and DHA has little or no effect on mortality or cardiovascular health (evidence mainly from supplement trials). Previous suggestions of benefits from EPA and DHA supplements appear to spring from trials with higher risk of bias. Low-quality evidence suggests ALA may slightly reduce CVD event and arrhythmia risk.

Omega-6 fats for the primary and secondary prevention of cardiovascular disease.

BACKGROUND: Omega-6 fats are polyunsaturated fats vital for many physiological functions, but their effect on cardiovascular disease (CVD) risk is debated. OBJECTIVES: To assess effects of increasing omega-6 fats (linoleic acid (LA), gamma-linolenic acid (GLA), dihomo-gamma-linolenic acid (DGLA) and arachidonic acid (AA)) on CVD and all-cause mortality. SEARCH METHODS: We searched CENTRAL, MEDLINE and Embase to May 2017 and clinicaltrials.gov and the World Health Organization International Clinical Trials Registry Platform to September 2016, without language restrictions. We checked trials included in relevant systematic reviews. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing higher versus lower omega-6 fat intake in adults with or without CVD, assessing effects over at least 12 months. We included full texts, abstracts, trials registry entries and unpublished studies. Outcomes were all-cause mortality, CVD mortality, CVD events, risk factors (blood lipids, adiposity, blood pressure), and potential adverse events. We excluded trials where we could not separate omega-6 fat effects from those of other dietary, lifestyle or medication interventions. DATA COLLECTION AND ANALYSIS: Two authors independently screened titles/abstracts, assessed trials for inclusion, extracted data, and assessed risk of bias of included trials. We wrote to authors of included studies. Meta-analyses used random-effects analysis, while sensitivity analyses used fixed-effects and limited analyses to trials at low summary risk of bias. We assessed GRADE quality of evidence for 'Summary of findings' tables. MAIN RESULTS: We included 19 RCTs in 6461 participants who were followed for one to eight years. Seven trials assessed the effects of supplemental GLA and 12 of LA, none DGLA or AA; the omega-6 fats usually displaced dietary saturated or monounsaturated fats. We assessed three RCTs as being at low summary risk of bias.Primary outcomes: we found low-quality evidence that increased intake of omega-6 fats may make little or no difference to all-cause mortality (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.88 to 1.12, 740 deaths, 4506 randomised, 10 trials) or CVD events (RR 0.97, 95% CI 0.81 to 1.15, 1404 people experienced events of 4962 randomised, 7 trials). We are uncertain whether increasing omega-6 fats affects CVD mortality (RR 1.09, 95% CI 0.76 to 1.55, 472 deaths, 4019 randomised, 7 trials), coronary heart disease events (RR 0.88, 95% CI 0.66 to 1.17, 1059 people with events of 3997 randomised, 7 trials), major adverse cardiac and cerebrovascular events (RR 0.84, 95% CI 0.59 to 1.20, 817 events, 2879 participants, 2 trials) or stroke (RR 1.36, 95% CI 0.45 to 4.11, 54 events, 3730 participants, 4 trials), as we assessed the evidence as being of very low quality. We found no evidence of dose-response or duration effects for any primary outcome, but there was a suggestion of greater protection in participants with lower baseline omega-6 intake across outcomes.Additional key outcomes: we found increased intake of omega-6 fats may reduce myocardial infarction (MI) risk (RR 0.88, 95% CI 0.76 to 1.02, 609 events, 4606 participants, 7 trials, low-quality evidence). High-quality evidence suggests increasing omega-6 fats reduces total serum cholesterol a little in the long term (mean difference (MD) -0.33 mmol/L, 95% CI -0.50 to -0.16, I2 = 81%; heterogeneity partially explained by dose, 4280 participants, 10 trials). Increasing omega-6 fats probably has little or no effect on adiposity (body mass index (BMI) MD -0.20 kg/m2, 95% CI -0.56 to 0.16, 371 participants, 1 trial, moderate-quality evidence). It may make little or no difference to serum triglycerides (MD -0.01 mmol/L, 95% CI -0.23 to 0.21, 834 participants, 5 trials), HDL (MD -0.01 mmol/L, 95% CI -0.03 to 0.02, 1995 participants, 4 trials) or low-density lipoprotein (MD -0.04 mmol/L, 95% CI -0.21 to 0.14, 244 participants, 2 trials, low-quality evidence). AUTHORS' CONCLUSIONS: This is the most extensive systematic assessment of effects of omega-6 fats on cardiovascular health, mortality, lipids and adiposity to date, using previously unpublished data. We found no evidence that increasing omega-6 fats reduces cardiovascular outcomes other than MI, where 53 people may need to increase omega-6 fat intake to prevent 1 person from experiencing MI. Although benefits of omega-6 fats remain to be proven, increasing omega-6 fats may be of benefit in people at high risk of MI. Increased omega-6 fats reduce serum total cholesterol but not other blood fat fractions or adiposity.

Polyunsaturated fatty acids for the primary and secondary prevention of cardiovascular disease.

BACKGROUND: Evidence on the health effects of total polyunsaturated fatty acids (PUFA) is equivocal. Fish oils are rich in omega-3 PUFA and plant oils in omega-6 PUFA. Evidence suggests that increasing PUFA-rich foods, supplements or supplemented foods can reduce serum cholesterol, but may increase body weight, so overall cardiovascular effects are unclear. OBJECTIVES: To assess effects of increasing total PUFA intake on cardiovascular disease and all-cause mortality, lipids and adiposity in adults. SEARCH METHODS: We searched CENTRAL, MEDLINE and Embase to April 2017 and clinicaltrials.gov and the World Health Organization International Clinical Trials Registry Platform to September 2016, without language restrictions. We checked trials included in relevant systematic reviews. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing higher with lower PUFA intakes in adults with or without cardiovascular disease that assessed effects over 12 months or longer. We included full texts, abstracts, trials registry entries and unpublished data. Outcomes were all-cause mortality, cardiovascular disease mortality and events, risk factors (blood lipids, adiposity, blood pressure), and adverse events. We excluded trials where we could not separate effects of PUFA intake from other dietary, lifestyle or medication interventions. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts, assessed trials for inclusion, extracted data, and assessed risk of bias. We wrote to authors of included trials for further data. Meta-analyses used random-effects analysis, sensitivity analyses included fixed-effects and limiting to low summary risk of bias. We assessed GRADE quality of evidence. MAIN RESULTS: We included 49 RCTs randomising 24,272 participants, with duration of one to eight years. Eleven included trials were at low summary risk of bias, 33 recruited participants without cardiovascular disease. Baseline PUFA intake was unclear in most trials, but 3.9% to 8% of total energy intake where reported. Most trials gave supplemental capsules, but eight gave dietary advice, eight gave supplemental foods such as nuts or margarine, and three used a combination of methods to increase PUFA.Increasing PUFA intake probably has little or no effect on all-cause mortality (risk 7.8% vs 7.6%, risk ratio (RR) 0.98, 95% confidence interval (CI) 0.89 to 1.07, 19,290 participants in 24 trials), but probably slightly reduces risk of coronary heart disease events from 14.2% to 12.3% (RR 0.87, 95% CI 0.72 to 1.06, 15 trials, 10,076 participants) and cardiovascular disease events from 14.6% to 13.0% (RR 0.89, 95% CI 0.79 to 1.01, 17,799 participants in 21 trials), all moderate-quality evidence. Increasing PUFA may slightly reduce risk of coronary heart disease death (6.6% to 6.1%, RR 0.91, 95% CI 0.78 to 1.06, 9 trials, 8810 participants) andstroke (1.2% to 1.1%, RR 0.91, 95% CI 0.58 to 1.44, 11 trials, 14,742 participants, though confidence intervals include important harms), but has little or no effect on cardiovascular mortality (RR 1.02, 95% CI 0.82 to 1.26, 16 trials, 15,107 participants) all low-quality evidence. Effects of increasing PUFA on major adverse cardiac and cerebrovascular events and atrial fibrillation are unclear as evidence is of very low quality.Increasing PUFA intake probably slightly decreases triglycerides (by 15%, MD -0.12 mmol/L, 95% CI -0.20 to -0.04, 20 trials, 3905 participants), but has little or no effect on total cholesterol (mean difference (MD) -0.12 mmol/L, 95% CI -0.23 to -0.02, 26 trials, 8072 participants), high-density lipoprotein (HDL) (MD -0.01 mmol/L, 95% CI -0.02 to 0.01, 18 trials, 4674 participants) or low-density lipoprotein (LDL) (MD -0.01 mmol/L, 95% CI -0.09 to 0.06, 15 trials, 3362 participants). Increasing PUFA probably has little or no effect on adiposity (body weight MD 0.76 kg, 95% CI 0.34 to 1.19, 12 trials, 7100 participants).Effects of increasing PUFA on serious adverse events such as pulmonary embolism and bleeding are unclear as the evidence is of very low quality. AUTHORS' CONCLUSIONS: This is the most extensive systematic review of RCTs conducted to date to assess effects of increasing PUFA on cardiovascular disease, mortality, lipids or adiposity. Increasing PUFA intake probably slightly reduces risk of coronary heart disease and cardiovascular disease events, may slightly reduce risk of coronary heart disease mortality and stroke (though not ruling out harms), but has little or no effect on all-cause or cardiovascular disease mortality. The mechanism may be via TG reduction.

Omega-6 fats for the primary and secondary prevention of cardiovascular disease.

BACKGROUND: Omega-6 fats are polyunsaturated fats vital for many physiological functions, but their effect on cardiovascular disease (CVD) risk is debated. OBJECTIVES: To assess effects of increasing omega-6 fats (linoleic acid (LA), gamma-linolenic acid (GLA), dihomo-gamma-linolenic acid (DGLA) and arachidonic acid (AA)) on CVD and all-cause mortality. SEARCH METHODS: We searched CENTRAL, MEDLINE and Embase to May 2017 and clinicaltrials.gov and the World Health Organization International Clinical Trials Registry Platform to September 2016, without language restrictions. We checked trials included in relevant systematic reviews. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing higher versus lower omega-6 fat intake in adults with or without CVD, assessing effects over at least 12 months. We included full texts, abstracts, trials registry entries and unpublished studies. Outcomes were all-cause mortality, CVD mortality, CVD events, risk factors (blood lipids, adiposity, blood pressure), and potential adverse events. We excluded trials where we could not separate omega-6 fat effects from those of other dietary, lifestyle or medication interventions. DATA COLLECTION AND ANALYSIS: Two authors independently screened titles/abstracts, assessed trials for inclusion, extracted data, and assessed risk of bias of included trials. We wrote to authors of included studies. Meta-analyses used random-effects analysis, while sensitivity analyses used fixed-effects and limited analyses to trials at low summary risk of bias. We assessed GRADE quality of evidence for 'Summary of findings' tables. MAIN RESULTS: We included 19 RCTs in 6461 participants who were followed for one to eight years. Seven trials assessed the effects of supplemental GLA and 12 of LA, none DGLA or AA; the omega-6 fats usually displaced dietary saturated or monounsaturated fats. We assessed three RCTs as being at low summary risk of bias.Primary outcomes: we found low-quality evidence that increased intake of omega-6 fats may make little or no difference to all-cause mortality (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.88 to 1.12, 740 deaths, 4506 randomised, 10 trials) or CVD events (RR 0.97, 95% CI 0.81 to 1.15, 1404 people experienced events of 4962 randomised, 7 trials). We are uncertain whether increasing omega-6 fats affects CVD mortality (RR 1.09, 95% CI 0.76 to 1.55, 472 deaths, 4019 randomised, 7 trials), coronary heart disease events (RR 0.88, 95% CI 0.66 to 1.17, 1059 people with events of 3997 randomised, 7 trials), major adverse cardiac and cerebrovascular events (RR 0.84, 95% CI 0.59 to 1.20, 817 events, 2879 participants, 2 trials) or stroke (RR 1.36, 95% CI 0.45 to 4.11, 54 events, 3730 participants, 4 trials), as we assessed the evidence as being of very low quality. We found no evidence of dose-response or duration effects for any primary outcome, but there was a suggestion of greater protection in participants with lower baseline omega-6 intake across outcomes.Additional key outcomes: we found increased intake of omega-6 fats may reduce myocardial infarction (MI) risk (RR 0.88, 95% CI 0.76 to 1.02, 609 events, 4606 participants, 7 trials, low-quality evidence). High-quality evidence suggests increasing omega-6 fats reduces total serum cholesterol a little in the long term (mean difference (MD) -0.33 mmol/L, 95% CI -0.50 to -0.16, I2 = 81%; heterogeneity partially explained by dose, 4280 participants, 10 trials). Increasing omega-6 fats probably has little or no effect on adiposity (body mass index (BMI) MD -0.20 kg/m2, 95% CI -0.56 to 0.16, 371 participants, 1 trial, moderate-quality evidence). It may make little or no difference to serum triglycerides (MD -0.01 mmol/L, 95% CI -0.23 to 0.21, 834 participants, 5 trials), HDL (MD -0.01 mmol/L, 95% CI -0.03 to 0.02, 1995 participants, 4 trials) or low-density lipoprotein (MD -0.04 mmol/L, 95% CI -0.21 to 0.14, 244 participants, 2 trials, low-quality evidence). AUTHORS' CONCLUSIONS: This is the most extensive systematic assessment of effects of omega-6 fats on cardiovascular health, mortality, lipids and adiposity to date, using previously unpublished data. We found no evidence that increasing omega-6 fats reduces cardiovascular outcomes other than MI, where 53 people may need to increase omega-6 fat intake to prevent 1 person from experiencing MI. Although benefits of omega-6 fats remain to be proven, increasing omega-6 fats may be of benefit in people at high risk of MI. Increased omega-6 fats reduce serum total cholesterol but not other blood fat fractions or adiposity.

Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease.

BACKGROUND: Researchers have suggested that 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)) benefit cardiovascular health. Guidelines recommend increasing omega-3-rich foods, and sometimes supplementation, but recent trials have not confirmed this. OBJECTIVES: To assess effects of increased intake of fish- and plant-based omega-3 for all-cause mortality, cardiovascular (CVD) events, adiposity and lipids. SEARCH METHODS: We searched CENTRAL, MEDLINE and Embase to April 2017, plus ClinicalTrials.gov and World Health Organization International Clinical Trials Registry to September 2016, with no language restrictions. We handsearched systematic review references and bibliographies and contacted authors. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that lasted at least 12 months and compared supplementation and/or advice to increase LCn3 or ALA intake versus usual or lower intake. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies 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 79 RCTs (112,059 participants) in this review update and found that 25 were at low summary risk of bias. Trials were of 12 to 72 months' duration and included adults at varying cardiovascular risk, mainly in high-income countries. Most studies assessed LCn3 supplementation with capsules, but some used LCn3- or ALA-rich or enriched foods or dietary advice compared to placebo or usual diet.Meta-analysis and sensitivity analyses suggested little or no effect of increasing LCn3 on all-cause mortality (RR 0.98, 95% CI 0.90 to 1.03, 92,653 participants; 8189 deaths in 39 trials, high-quality evidence), cardiovascular mortality (RR 0.95, 95% CI 0.87 to 1.03, 67,772 participants; 4544 CVD deaths in 25 RCTs), cardiovascular events (RR 0.99, 95% CI 0.94 to 1.04, 90,378 participants; 14,737 people experienced events in 38 trials, high-quality evidence), coronary heart disease (CHD) mortality (RR 0.93, 95% CI 0.79 to 1.09, 73,491 participants; 1596 CHD deaths in 21 RCTs), stroke (RR 1.06, 95% CI 0.96 to 1.16, 89,358 participants; 1822 strokes in 28 trials) or arrhythmia (RR 0.97, 95% CI 0.90 to 1.05, 53,796 participants; 3788 people experienced arrhythmia in 28 RCTs). There was a suggestion that LCn3 reduced CHD events (RR 0.93, 95% CI 0.88 to 0.97, 84,301 participants; 5469 people experienced CHD events in 28 RCTs); however, this was not maintained in sensitivity analyses - LCn3 probably makes little or no difference to CHD event risk. All evidence was of moderate GRADE quality, except as noted.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, 5 RCTs),cardiovascular mortality (RR 0.96, 95% CI 0.74 to 1.25, 18,619 participants; 219 cardiovascular deaths, 4 RCTs), and it may make little or no difference to CHD events (RR 1.00, 95% CI 0.80 to 1.22, 19,061 participants, 397 CHD events, 4 RCTs, low-quality evidence). However, increased ALA may slightly reduce risk of cardiovascular events (from 4.8% to 4.7%, RR 0.95, 95% CI 0.83 to 1.07, 19,327 participants; 884 CVD events, 5 RCTs, low-quality evidence), and probably reduces risk of CHD mortality (1.1% to 1.0%, RR 0.95, 95% CI 0.72 to 1.26, 18,353 participants; 193 CHD deaths, 3 RCTs), and arrhythmia (3.3% to 2.6%, RR 0.79, 95% CI 0.57 to 1.10, 4,837 participants; 141 events, 1 RCT). Effects on stroke are unclear.Sensitivity analysis retaining only trials at low summary risk of bias moved effect sizes towards the null (RR 1.0) for all LCn3 primary outcomes except arrhythmias, but for most ALA outcomes, effect sizes moved to suggest protection. LCn3 funnel plots suggested that adding in missing studies/results would move effect sizes towards null for most primary outcomes. There were no dose or duration effects in subgrouping or meta-regression.There was no evidence that increasing LCn3 or ALA altered serious adverse events, adiposity or lipids, although LCn3 slightly reduced triglycerides and increased HDL. ALA probably reduces HDL (high- or moderate-quality evidence). AUTHORS' CONCLUSIONS: This is the most extensive systematic assessment of effects of omega-3 fats on cardiovascular health to date. Moderate- and high-quality evidence suggests that increasing EPA and DHA has little or no effect on mortality or cardiovascular health (evidence mainly from supplement trials). Previous suggestions of benefits from EPA and DHA supplements appear to spring from trials with higher risk of bias. Low-quality evidence suggests ALA may slightly reduce CVD event risk, CHD mortality and arrhythmia.

Polyunsaturated fatty acids for the primary and secondary prevention of cardiovascular disease.

BACKGROUND: Evidence on the health effects of total polyunsaturated fatty acids (PUFA) is equivocal. Fish oils are rich in omega-3 PUFA and plant oils in omega-6 PUFA. Evidence suggests that increasing PUFA-rich foods, supplements or supplemented foods can reduce serum cholesterol, but may increase body weight, so overall cardiovascular effects are unclear. OBJECTIVES: To assess effects of increasing total PUFA intake on cardiovascular disease and all-cause mortality, lipids and adiposity in adults. SEARCH METHODS: We searched CENTRAL, MEDLINE and Embase to April 2017 and clinicaltrials.gov and the World Health Organization International Clinical Trials Registry Platform to September 2016, without language restrictions. We checked trials included in relevant systematic reviews. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing higher with lower PUFA intakes in adults with or without cardiovascular disease that assessed effects over 12 months or longer. We included full texts, abstracts, trials registry entries and unpublished data. Outcomes were all-cause mortality, cardiovascular disease mortality and events, risk factors (blood lipids, adiposity, blood pressure), and adverse events. We excluded trials where we could not separate effects of PUFA intake from other dietary, lifestyle or medication interventions. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts, assessed trials for inclusion, extracted data, and assessed risk of bias. We wrote to authors of included trials for further data. Meta-analyses used random-effects analysis, sensitivity analyses included fixed-effects and limiting to low summary risk of bias. We assessed GRADE quality of evidence. MAIN RESULTS: We included 49 RCTs randomising 24,272 participants, with duration of one to eight years. Eleven included trials were at low summary risk of bias, 33 recruited participants without cardiovascular disease. Baseline PUFA intake was unclear in most trials, but 3.9% to 8% of total energy intake where reported. Most trials gave supplemental capsules, but eight gave dietary advice, eight gave supplemental foods such as nuts or margarine, and three used a combination of methods to increase PUFA.Increasing PUFA intake probably has little or no effect on all-cause mortality (risk 7.8% vs 7.6%, risk ratio (RR) 0.98, 95% confidence interval (CI) 0.89 to 1.07, 19,290 participants in 24 trials), but probably slightly reduces risk of coronary heart disease events from 14.2% to 12.3% (RR 0.87, 95% CI 0.72 to 1.06, 15 trials, 10,076 participants) and cardiovascular disease events from 14.6% to 13.0% (RR 0.89, 95% CI 0.79 to 1.01, 17,799 participants in 21 trials), all moderate-quality evidence. Increasing PUFA may slightly reduce risk of coronary heart disease death (6.6% to 6.1%, RR 0.91, 95% CI 0.78 to 1.06, 9 trials, 8810 participants) andstroke (1.2% to 1.1%, RR 0.91, 95% CI 0.58 to 1.44, 11 trials, 14,742 participants, though confidence intervals include important harms), but has little or no effect on cardiovascular mortality (RR 1.02, 95% CI 0.82 to 1.26, 16 trials, 15,107 participants) all low-quality evidence. Effects of increasing PUFA on major adverse cardiac and cerebrovascular events and atrial fibrillation are unclear as evidence is of very low quality.Increasing PUFA intake slightly reduces total cholesterol (mean difference (MD) -0.12 mmol/L, 95% CI -0.23 to -0.02, 26 trials, 8072 participants) and probably slightly decreases triglycerides (MD -0.12 mmol/L, 95% CI -0.20 to -0.04, 20 trials, 3905 participants), but has little or no effect on high-density lipoprotein (HDL) (MD -0.01 mmol/L, 95% CI -0.02 to 0.01, 18 trials, 4674 participants) or low-density lipoprotein (LDL) (MD -0.01 mmol/L, 95% CI -0.09 to 0.06, 15 trials, 3362 participants). Increasing PUFA probably causes slight weight gain (MD 0.76 kg, 95% CI 0.34 to 1.19, 12 trials, 7100 participants).Effects of increasing PUFA on serious adverse events such as pulmonary embolism and bleeding are unclear as the evidence is of very low quality. AUTHORS' CONCLUSIONS: This is the most extensive systematic review of RCTs conducted to date to assess effects of increasing PUFA on cardiovascular disease, mortality, lipids or adiposity. Increasing PUFA intake probably slightly reduces risk of coronary heart disease and cardiovascular disease events, may slightly reduce risk of coronary heart disease mortality and stroke (though not ruling out harms), but has little or no effect on all-cause or cardiovascular disease mortality. The mechanism may be via lipid reduction, but increasing PUFA probably slightly increases weight.