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.

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.

Reduced or modified dietary fat for preventing cardiovascular disease.

BACKGROUND: Reduction and modification of dietary fats have differing effects on cardiovascular risk factors (such as serum cholesterol), but their effects on important health outcomes are less clear. OBJECTIVE: To assess the effect of reduction and/or modification of dietary fats on mortality, cardiovascular mortality, cardiovascular morbidity and individual outcomes including myocardial infarction, stroke and cancer diagnoses in randomised clinical trials of at least 6 months duration. SEARCH METHODS: For this review update, the Cochrane Central Register of Controlled Trials (CENTRAL), Medline and Embase, were searched through to June 2010. References of Included studies and reviews were also checked. SELECTION CRITERIA: Trials fulfilled the following criteria: 1) randomized with appropriate control group, 2) intention to reduce or modify fat or cholesterol intake (excluding exclusively omega-3 fat interventions), 3) not multi factorial, 4) adult humans with or without cardiovascular disease, 5) intervention at least six months, 6) mortality or cardiovascular morbidity data available. DATA COLLECTION AND ANALYSIS: Participant numbers experiencing health outcomes in each arm were extracted independently in duplicate and random effects meta-analyses, meta-regression, sub-grouping, sensitivity analyses and funnel plots were performed. MAIN RESULTS: This updated review suggested that reducing saturated fat by reducing and/or modifying dietary fat reduced the risk of cardiovascular events by 14% (RR 0.86, 95% CI 0.77 to 0.96, 24 comparisons, 65,508 participants of whom 7% had a cardiovascular event, I2 50%). Subgrouping suggested that this reduction in cardiovascular events was seen in studies of fat modification (not reduction - which related directly to the degree of effect on serum total and LDL cholesterol and triglycerides), of at least two years duration and in studies of men (not of women). There were no clear effects of dietary fat changes on total mortality (RR 0.98, 95% CI 0.93 to 1.04, 71,790 participants) or cardiovascular mortality (RR 0.94, 95% CI 0.85 to 1.04, 65,978 participants). This did not alter with sub-grouping or sensitivity analysis. Few studies compared reduced with modified fat diets, so direct comparison was not possible. AUTHORS' CONCLUSIONS: The findings are suggestive of a small but potentially important reduction in cardiovascular risk on modification of dietary fat, but not reduction of total fat, in longer trials. Lifestyle advice to all those at risk of cardiovascular disease and to lower risk population groups, should continue to include permanent reduction of dietary saturated fat and partial replacement by unsaturates. The ideal type of unsaturated fat is unclear.

Reduced or modified dietary fat for preventing cardiovascular disease

ABSTRACT: BACKGROUND: Reduction and modification of dietary fats have differing effects on cardiovascular risk factors (such as serum cholesterol), but their effects on important health outcomes are less clear. OBJECTIVE: To assess the effect of reduction and/or modification of dietary fats on mortality, cardiovascular mortality, cardiovascular morbidity and individual outcomes including myocardial infarction, stroke and cancer diagnoses in randomised clinical trials of at least 6 months duration. METHODS: Search methods: For this review update, the Cochrane Central Register of Controlled Trials (CENTRAL), Medline and Embase, were searched through to June 2010. References of Included studies and reviews were also checked. Selection criteria: Trials fulfilled the following criteria: 1) randomized with appropriate control group, 2) intention to reduce or modify fat or cholesterol intake (excluding exclusively omega-3 fat interventions), 3) not multi factorial, 4) adult humans with or without cardiovascular disease, 5) intervention at least six months, 6) mortality or cardiovascular morbidity data available. Data collection and analysis: Participant numbers experiencing health outcomes in each arm were extracted independently in duplicate and random effects meta-analyses, meta-regression, sub-grouping, sensitivity analyses and funnel plots were performed. MAIN RESULTS: This updated review suggested that reducing saturated fat by reducing and/or modifying dietary fat reduced the risk of cardiovascular events by 14% (RR 0.86, 95% CI 0.77 to 0.96, 24 comparisons, 65,508 participants of whom 7% had a cardiovascular event, I2 50%). Subgrouping suggested that this reduction in cardiovascular events was seen in studies of fat modification (not reduction - which related directly to the degree of effect on serum total and LDL cholesterol and triglycerides), of at least two years duration and in studies of men (not of women). There were no clear effects of dietary fat changes on total mortality (RR 0.98, 95% CI 0.93 to 1.04, 71,790 participants) or cardiovascular mortality (RR 0.94, 95% CI 0.85 to 1.04, 65,978 participants). This did not alter with sub-grouping or sensitivity analysis. Few studies compared reduced with modified fat diets, so direct comparison was not possible. AUTHORS' CONCLUSIONS: The findings are suggestive of a small but potentially important reduction in cardiovascular risk on modification of dietary fat, but not reduction of total fat, in longer trials. Lifestyle advice to all those at risk of cardiovascular disease and to lower risk population groups, should continue to include permanent reduction of dietary saturated fat and partial replacement by unsaturates. The ideal type of unsaturated fat is unclear.

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 that are lost in the diet are more helpfully replaced by polyunsaturated fats, monounsaturated fats, carbohydrate or protein. This review is part of a series split from and updating an overarching review. OBJECTIVES: To assess the effect of reducing saturated fat intake and replacing it with carbohydrate (CHO), polyunsaturated (PUFA) or 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 5 March 2014. We also checked references of included studies and reviews. SELECTION CRITERIA: Trials fulfilled the following criteria: 1) randomised with appropriate control group; 2) intention to reduce saturated fat intake OR intention to alter dietary fats and achieving a reduction in saturated fat; 3) not multifactorial; 4) adult humans with or without cardiovascular disease (but not acutely ill, pregnant or breastfeeding); 5) intervention at least 24 months; 6) mortality or cardiovascular morbidity data available. DATA COLLECTION AND ANALYSIS: Two review authors working independently extracted participant numbers experiencing health outcomes in each arm, and we performed random-effects meta-analyses, meta-regression, subgrouping, sensitivity analyses and funnel plots. MAIN RESULTS: We include 15 randomised controlled trials (RCTs) (17 comparisons, ˜59,000 participants), which used a variety of interventions from providing all food to advice on how to reduce saturated fat. The included long-term trials suggested that reducing dietary saturated fat reduced the risk of cardiovascular events by 17% (risk ratio (RR) 0.83; 95% confidence interval (CI) 0.72 to 0.96, 13 comparisons, 53,300 participants of whom 8% had a cardiovascular event, I² 65%, GRADE moderate quality of evidence), but effects on all-cause mortality (RR 0.97; 95% CI 0.90 to 1.05; 12 trials, 55,858 participants) and cardiovascular mortality (RR 0.95; 95% CI 0.80 to 1.12, 12 trials, 53,421 participants) were less clear (both GRADE moderate quality of evidence). There was some evidence that reducing saturated fats reduced the risk of myocardial infarction (fatal and non-fatal, RR 0.90; 95% CI 0.80 to 1.01; 11 trials, 53,167 participants), but evidence for non-fatal myocardial infarction (RR 0.95; 95% CI 0.80 to 1.13; 9 trials, 52,834 participants) was unclear and there were no clear effects on stroke (any stroke, RR 1.00; 95% CI 0.89 to 1.12; 8 trials, 50,952 participants). These relationships did not alter with sensitivity analysis. Subgrouping suggested that the reduction in cardiovascular events was seen in studies that primarily replaced saturated fat calories with polyunsaturated fat, and no effects were seen in studies replacing saturated fat with carbohydrate or protein, but effects in studies replacing with monounsaturated fats were unclear (as we located only one small trial). Subgrouping and meta-regression suggested that the degree of reduction in cardiovascular events was related to the degree of reduction of serum total cholesterol, and there were suggestions of greater protection with greater saturated fat reduction or greater increase in polyunsaturated and monounsaturated fats. There was no evidence of harmful effects of reducing saturated fat intakes on cancer mortality, cancer diagnoses or blood pressure, while there was some evidence of improvements in weight and BMI. AUTHORS' CONCLUSIONS: The findings of this updated review are suggestive of a small but potentially important reduction in cardiovascular risk on reduction of saturated fat intake. Replacing the energy from saturated fat with polyunsaturated fat appears to be a useful strategy, and replacement with carbohydrate appears less useful, but effects of replacement with monounsaturated fat were unclear due to inclusion of only one small trial. This effect did not appear to alter by study duration, sex or baseline level of cardiovascular risk. Lifestyle advice to all those at risk of cardiovascular disease and to lower risk population groups should continue to include permanent reduction of dietary saturated fat and partial replacement by unsaturated fats. The ideal type of unsaturated fat is unclear.

Water-loss dehydration and aging.

This review defines water-loss and salt-loss dehydration. For older people serum osmolality appears the most appropriate gold standard for diagnosis of water-loss dehydration, but clear signs of early dehydration have not been developed. In older adults, lower muscle mass, reduced kidney function, physical and cognitive disabilities, blunted thirst, and polypharmacy all increase dehydration risk. Cross-sectional studies suggest a water-loss dehydration prevalence of 20-30% in this population. Water-loss dehydration is associated with higher mortality, morbidity and disability in older people, but evidence is still needed that this relationship is causal. There are a variety of ways we may be able to help older people reduce their risk of dehydration by recognising that they are not drinking enough, and being helped to drink more. Strategies to increase fluid intake in residential care homes include identifying and overcoming individual and institutional barriers to drinking, such as being worried about not reaching the toilet in time, physical inability to make or to reach drinks, and reduced social drinking and drinking pleasure. Research needs are discussed, some of which will be addressed by the FP7-funded NU-AGE (New dietary strategies addressing the specific needs of elderly population for a healthy ageing in Europe) trial.

EURRECA-Estimating iron requirements for deriving dietary reference values.

Currently, a factorial approach is used to derive reference values for iron. Calculations include the use of a bioavailability factor to convert the physiological requirement, derived from obligatory losses and requirements for growth and development, into a dietary intake value. A series of systematic reviews undertaken by the EURRECA Network of Excellence aimed to identify data that may increase the accuracy of factorial calculations across all population groups. The selection of robust data was guided by the use of standardized review methodology and the evidence-based selection of status biomarkers and dietary intake assessment techniques. Results corroborated the dearth of relevant factorial data, including whole-diet bioavailability data, and confirmed the need to continue extrapolating physiological requirements across population groups. Data were also unavailable that would allow reference values to be based on selected health outcomes associated with iron intake or status. Ideally, a series of observational and randomized controlled trial (RCT) studies need to be undertaken across all population groups and life stages to generate robust data for setting dietary reference values for iron. It will also be essential to include information on polymorphisms that potentially influence iron absorption and status in the derivation process.

EURRECA-Estimating selenium requirements for deriving dietary reference values.

Current reference values for selenium, an essential micronutrient, are based on the intake of selenium that is required to achieve maximal glutathione peroxidase activity in plasma or erythrocytes. In order to assess the evidence of relevance to setting dietary reference values for selenium, the EURRECA Network of Excellence focused on systematic searches, review, and evaluation of (i) selenium status biomarkers and evidence for relationships between intake and status biomarkers, (ii) selenium and health (including the effect of intake and/or status biomarkers on cancer risk, immune function, HIV, cognition, and fertility), (iii) bioavailability of selenium from the diet, and (iv) impact of genotype/single nucleotide polymorphisms on status or health outcomes associated with selenium. The main research outputs for selenium and future research priorities are discussed further in this review.

Green and black tea for the primary prevention of cardiovascular disease.

BACKGROUND: There is increasing evidence that both green and black tea are beneficial for cardiovascular disease (CVD) prevention. OBJECTIVES: To determine the effects of green and black tea on the primary prevention of CVD. SEARCH METHODS: We searched the following databases on 12 October 2012 without language restrictions: CENTRAL in The Cochrane Library, MEDLINE (OVID), EMBASE (OVID) and Web of Science (Thomson Reuters). We also searched trial registers, screened reference lists and contacted authors for additional information where necessary. SELECTION CRITERIA: Randomised controlled trials (RCTs) lasting at least three months involving healthy adults or those at high risk of CVD. Trials investigated the intake of green tea, black tea or tea extracts. The comparison group was no intervention, placebo or minimal intervention. The outcomes of interest were CVD clinical events and major CVD risk factors. Any trials involving multifactorial lifestyle interventions or focusing on weight loss were excluded to avoid confounding. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, abstracted data and assessed the risk of bias. Trials of green tea were analysed separately from trials of black tea. MAIN RESULTS: We identified 11 RCTs with a total of 821 participants, two trials awaiting classification and one ongoing trial. Seven trials examined a green tea intervention and four examined a black tea intervention. Dosage and form of both green and black tea differed between trials. The ongoing trial is examining the effects of green tea powder capsules.No studies reported cardiovascular events.Black tea was found to produce statistically significant reductions in low-density lipoprotein (LDL) cholesterol (mean difference (MD) -0.43 mmol/L, 95% confidence interval (CI) -0.56 to -0.31) and blood pressure (systolic blood pressure (SBP): MD -1.85 mmHg, 95% CI -3.21 to -0.48. Diastolic blood pressure (DBP): MD -1.27 mmHg, 95% CI -3.06 to 0.53) over six months, stable to sensitivity analysis, but only a small number of trials contributed to each analysis and studies were at risk of bias.Green tea was also found to produce statistically significant reductions in total cholesterol (MD -0.62 mmol/L, 95% CI -0.77 to -0.46), LDL cholesterol (MD -0.64 mmol/L, 95% CI -0.77 to -0.52) and blood pressure (SBP: MD -3.18 mmHg, 95% CI -5.25 to -1.11; DBP: MD -3.42, 95% CI -4.54 to -2.30), but only a small number of studies contributed to each analysis, and results were not stable to sensitivity analysis. When both tea types were analysed together they showed favourable effects on LDL cholesterol (MD -0.48 mmol/L, 95% CI -0.61 to -0.35) and blood pressure (SBP: MD -2.25 mmHg, 95% CI -3.39 to -1.11; DBP: MD -2.81 mmHg, 95% CI -3.77 to -1.86). Adverse events were measured in five trials and included a diagnosis of prostate cancer, hospitalisation for influenza, appendicitis and retinal detachment but these are unlikely to be directly attributable to the intervention. AUTHORS' CONCLUSIONS: There are very few long-term studies to date examining green or black tea for the primary prevention of CVD. The limited evidence suggests that tea has favourable effects on CVD risk factors, but due to the small number of trials contributing to each analysis the results should be treated with some caution and further high quality trials with longer-term follow-up are needed to confirm this.

The absorption of iron from whole diets: a systematic review.

BACKGROUND: Absorption factors are required to convert physiologic requirements for iron into Dietary Reference Values, but the absorption from single meals cannot be used to estimate dietary iron absorption. OBJECTIVE: The objective was to conduct a systematic review of iron absorption from whole diets. DESIGN: A structured search was completed by using the Medline, EMBASE, and Cochrane CENTRAL databases from inception to November 2011. Formal inclusion and exclusion criteria were applied, and data extraction, validity assessment, and meta-analyses were undertaken. RESULTS: Nineteen studies from the United States, Europe, and Mexico were included. Absorption from diets was higher with an enhancer (standard mean difference: 0.53; 95% CI: 0.21, 0.85; P = 0.001) and was also higher when compared with low-bioavailability diets (standard mean difference: 0.96; 95% CI: 0.51, 1.41; P < 0.0001); however, single inhibitors did not reduce absorption (possibly because of the limited number of studies and participants and their heterogeneity). A regression equation to calculate iron absorption was derived by pooling data for iron status (serum and plasma ferritin) and dietary enhancers and inhibitors from 58 individuals (all from US studies): log[nonheme-iron absorption, %] = -0.73 log[ferritin, µg/L] + 0.11 [modifier] + 1.82. In individuals with serum ferritin concentrations from 6 to 80 µg/L, predicted absorption ranged from 2.1% to 23.0%. CONCLUSIONS: Large variations were observed in mean nonheme-iron absorption (0.7-22.9%) between studies, which depended on iron status (diet had a greater effect at low serum and plasma ferritin concentrations) and dietary enhancers and inhibitors. Iron absorption was predicted from serum ferritin concentrations and dietary modifiers by using a regression equation. Extrapolation of these findings to developing countries and to men and women of different ages will require additional high-quality controlled trials.

Effect of iron intake on iron status: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The response of status biomarkers to an increase in iron supply depends on several physiologic and environmental factors, which make it difficult to predict the outcome of an intervention. OBJECTIVE: We assessed effects of baseline iron status, sex, menopausal status, duration of intervention, iron form, and daily dose on the change in iron status in response to iron supplementation. DESIGN: A systematic review of randomized controlled trials (RCTs) of iron-supplementation and -fortification trials that assessed effects on hemoglobin, serum ferritin (SF), soluble transferrin receptor, or body iron was conducted. Subgrouping and straight-line and curved metaregression were used to describe the magnitude and dose-responsiveness of effect modifiers with respect to changes in status. RESULTS: Forty-one RCTs were included; none of the RCTs were judged at low risk of bias. Random-effects meta-analyses showed that iron supplementation significantly improved iron status but with high levels of heterogeneity. Metaregression explained approximately one-quarter of between-study variance in effect size. There were clear effects on SF with study duration (increase in SF concentration/wk: 0.51 µg/L; 95% CI: 0.02, 1.00 µg/L; P = 0.04) and dose (increase in SF concentration/g Fe: 0.10 µg/L; 95% CI: 0.01, 0.20 µg/L; P = 0.036) and on hemoglobin concentrations with baseline iron status [-0.08 g/dL (95% CI: 0.15, 0.00 g/dL) per 10-µg/L increase in baseline SF concentration; P = 0.02]. Insufficient data were available to assess effects on body iron, sex, or menopausal status. CONCLUSION: Quantitative relations between baseline iron status, study duration, and iron dose on changes in iron-status biomarkers, which were generated from the meta-analyses, can be used to predict effects of trials of iron supplementation and fortification and to design iron-intervention programs.

Selenium and prostate cancer: systematic review and meta-analysis.

BACKGROUND: Prostate cancer is a growing public health problem. Several human studies have shown a potentially protective effect of selenium, but the conclusions from published reports are inconsistent. OBJECTIVE: The objective was to examine the evidence for relations between selenium intake, selenium status, and prostate cancer risk. DESIGN: This was a systematic review and meta-analysis of randomized controlled trials, case-control studies, and prospective cohort studies. The World Cancer Research Fund/American Institute for Cancer Research Continuous Update Project database was searched up to September 2010. The studies included reported measurements of selenium intake or status (plasma, serum, or toenail selenium), assessments of prostate cancer cases (number of events), and the RR in the adult population. Meta-analyses were performed, and study quality, heterogeneity, and small study effects were assessed. Dose-response meta-analyses were used, with restricted cubic splines and fractional polynomials for nonlinear trends, to investigate the association between selenium status and prostate cancer risk. RESULTS: Twelve studies with a total of 13,254 participants and 5007 cases of prostate cancer were included. The relation between plasma/serum selenium and prostate cancer in a nonlinear dose-response meta-analysis showed that the risk decreased with increasing plasma/serum selenium up to 170 ng/mL. Three high-quality studies included in the meta-analysis of toenail selenium and cancer risk indicated a reduction in prostate cancer risk (estimated RR: 0.29; 95% CI: 0.14, 0.61) with a toenail selenium concentration between 0.85 and 0.94 µg/g. CONCLUSION: The relation between selenium status and decreased prostate cancer risk was examined over a relatively narrow range of selenium status; further studies in low-selenium populations are required.

Reduced or modified dietary fat for preventing cardiovascular disease.

BACKGROUND: Reduction and modification of dietary fats have differing effects on cardiovascular risk factors (such as serum cholesterol), but their effects on important health outcomes are less clear. OBJECTIVES: To assess the effect of reduction and/or modification of dietary fats on mortality, cardiovascular mortality, cardiovascular morbidity and individual outcomes including myocardial infarction, stroke and cancer diagnoses in randomised clinical trials of at least 6 months duration. SEARCH METHODS: For this review update, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE, were searched through to June 2010. References of Included studies and reviews were also checked. SELECTION CRITERIA: Trials fulfilled the following criteria: 1) randomised with appropriate control group, 2) intention to reduce or modify fat or cholesterol intake (excluding exclusively omega-3 fat interventions), 3) not multi factorial, 4) adult humans with or without cardiovascular disease, 5) intervention at least six months, 6) mortality or cardiovascular morbidity data available. DATA COLLECTION AND ANALYSIS: Participant numbers experiencing health outcomes in each arm were extracted independently in duplicate and random effects meta-analyses, meta-regression, sub-grouping, sensitivity analyses and funnel plots were performed. MAIN RESULTS: This updated review suggested that reducing saturated fat by reducing and/or modifying dietary fat reduced the risk of cardiovascular events by 14% (RR 0.86, 95% CI 0.77 to 0.96, 24 comparisons, 65,508 participants of whom 7% had a cardiovascular event, I(2) 50%). Subgrouping suggested that this reduction in cardiovascular events was seen in studies of fat modification (not reduction - which related directly to the degree of effect on serum total and LDL cholesterol and triglycerides), of at least two years duration and in studies of men (not of women). There were no clear effects of dietary fat changes on total mortality (RR 0.98, 95% CI 0.93 to 1.04, 71,790 participants) or cardiovascular mortality (RR 0.94, 95% CI 0.85 to 1.04, 65,978 participants). This did not alter with sub-grouping or sensitivity analysis.Few studies compared reduced with modified fat diets, so direct comparison was not possible. AUTHORS' CONCLUSIONS: The findings are suggestive of a small but potentially important reduction in cardiovascular risk on modification of dietary fat, but not reduction of total fat, in longer trials. Lifestyle advice to all those at risk of cardiovascular disease and to lower risk population groups, should continue to include permanent reduction of dietary saturated fat and partial replacement by unsaturates. The ideal type of unsaturated fat is unclear.

Reduced or modified dietary fat for preventing cardiovascular disease.

BACKGROUND: Reduction and modification of dietary fats have differing effects on cardiovascular risk factors (such as serum cholesterol), but their effects on important health outcomes are less clear. OBJECTIVES: To assess the effect of reduction and/or modification of dietary fats on mortality, cardiovascular mortality, cardiovascular morbidity and individual outcomes including myocardial infarction, stroke and cancer diagnoses in randomised clinical trials of at least 6 months duration. SEARCH STRATEGY: For this review update, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE, were searched through to June 2010. References of Included studies and reviews were also checked. SELECTION CRITERIA: Trials fulfilled the following criteria: 1) randomised with appropriate control group, 2) intention to reduce or modify fat or cholesterol intake (excluding exclusively omega-3 fat interventions), 3) not multi factorial, 4) adult humans with or without cardiovascular disease, 5) intervention at least six months, 6) mortality or cardiovascular morbidity data available. DATA COLLECTION AND ANALYSIS: Participant numbers experiencing health outcomes in each arm were extracted independently in duplicate and random effects meta-analyses, meta-regression, sub-grouping, sensitivity analyses and funnel plots were performed. MAIN RESULTS: This updated review suggested that reducing saturated fat by reducing and/or modifying dietary fat reduced the risk of cardiovascular events by 14% (RR 0.86, 95% CI 0.77 to 0.96, 24 comparisons, 65,508 participants of whom 7% had a cardiovascular event, I(2) 50%). Subgrouping suggested that this reduction in cardiovascular events was seen in studies of fat modification (not reduction - which related directly to the degree of effect on serum total and LDL cholesterol and triglycerides), of at least two years duration and in studies of men (not of women). There were no clear effects of dietary fat changes on total mortality (RR 0.98, 95% CI 0.93 to 1.04, 71,790 participants) or cardiovascular mortality (RR 0.94, 95% CI 0.85 to 1.04, 65,978 participants). This did not alter with sub-grouping or sensitivity analysis.Few studies compared reduced with modified fat diets, so direct comparison was not possible. AUTHORS' CONCLUSIONS: The findings are suggestive of a small but potentially important reduction in cardiovascular risk on modification of dietary fat, but not reduction of total fat, in longer trials. Lifestyle advice to all those at risk of cardiovascular disease and to lower risk population groups, should continue to include permanent reduction of dietary saturated fat and partial replacement by unsaturates. The ideal type of unsaturated fat is unclear.

A survey of orthopaedic journal editors determining the criteria of manuscript selection for publication.

BACKGROUND: To investigate the characteristics of editors and criteria used by orthopaedic journal editors in assessing submitted manuscripts. METHODS: Between 2008 to 2009 all 70 editors of Medline listed orthopaedic journals were approached prospectively with a questionnaire to determine the criteria used in assessing manuscripts for publication. RESULTS: There was a 42% response rate. There was 1 female editor and the rest were male with 57% greater than 60 years of age. 67% of the editors worked in university teaching hospitals and 90% of publications were in English. The review process differed between journals with 59% using a review proforma, 52% reviewing an anonymised manuscript, 76% using a routine statistical review and 59% of journals used 2 reviewers routinely. In 89% of the editors surveyed, the editor was able to overrule the final decision of the reviewers. Important design factors considered for manuscript acceptance were that the study conclusions were justified (80%), that the statistical analysis was appropriate (76%), that the findings could change practice (72%). The level of evidence (70%) and type of study (62%) were deemed less important. When asked what factors were important in the manuscript influencing acceptance, 73% cited an understandable manuscript, 53% cited a well written manuscript and 50% a thorough literature review as very important factors. CONCLUSIONS: The editorial and review process in orthopaedic journals uses different approaches. There may be a risk of language bias among editors of orthopaedic journals with under-representation of non-English publications in the orthopaedic literature.

Feeding interventions for growth and development in infants with cleft lip, cleft palate or cleft lip and palate.

BACKGROUND: Cleft lip and cleft palate are common birth defects, affecting about one baby of every 700 born. Feeding these babies is an immediate concern and there is evidence of delay in growth of children with a cleft as compared to those without clefting. In an effort to combat reduced weight for height, a variety of advice and devices are recommended to aid feeding of babies with clefts. OBJECTIVES: This review aims to assess the effects of these feeding interventions in babies with cleft lip and/or palate on growth, development and parental satisfaction. SEARCH STRATEGY: The following electronic databases were searched: the Cochrane Oral Health Group Trials Register (to 27 October 2010), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 4), MEDLINE via OVID (1950 to 27 October 2010), EMBASE via OVID (1980 to 27 October 2010), PsycINFO via OVID (1950 to 27 October 2010) and CINAHL via EBSCO (1980 to 27 October 2010). Attempts were made to identify both unpublished and ongoing studies. There was no restriction with regard to language of publication. SELECTION CRITERIA: Studies were included if they were randomised controlled trials (RCTs) of feeding interventions for babies born with cleft lip, cleft palate or cleft lip and palate up to the age of 6 months (from term). DATA COLLECTION AND ANALYSIS: Studies were assessed for relevance independently and in duplicate. All studies meeting the inclusion criteria were data extracted and assessed for validity independently by each member of the review team. Authors were contacted for clarification or missing information whenever possible. MAIN RESULTS: Five RCTs with a total of 292 babies, were included in the review. Comparisons made within the RCTs were squeezable versus rigid feeding bottles (two studies), breastfeeding versus spoon-feeding (one study) and maxillary plate versus no plate (two studies). No statistically significant differences were shown for any of the primary outcomes when comparing bottle types, although squeezable bottles were less likely to require modification. No difference was shown for infants fitted with a maxillary plate compared to no plate. However, there was some evidence of an effect on weight at 6 weeks post-surgery in favour of breastfeeding when compared to spoon-feeding (mean difference 0.47; 95% confidence interval 0.20 to 0.74). AUTHORS' CONCLUSIONS: Squeezable bottles appear easier to use than rigid feeding bottles for babies born with clefts of the lip and/or palate, however, there is no evidence of a difference in growth outcomes between the bottle types. There is weak evidence that breastfeeding is better than spoon-feeding following surgery for cleft. There was no evidence to suggest that maxillary plates assist growth in babies with clefts of the palate. No evidence was found to assess the use of any types of maternal advice and/or support for these babies.

Urinary metabolites as biomarkers of polyphenol intake in humans: a systematic review.

BACKGROUND: To identify associations between polyphenol intake and health and disease outcomes in cohort studies, it is important to identify biomarkers of intake for the various compounds commonly consumed as part of the diet. OBJECTIVE: The objective of this systematic review was to assess the usefulness of polyphenol metabolites excreted in urine as biomarkers of polyphenol intake in humans. DESIGN: The method included a structured search strategy for polyphenol intervention studies on Ovid MEDLINE, EMBASE (Ovid), and Cochrane databases; formal inclusion and exclusion criteria; data extraction into an Access database; validity assessment; and meta-analysis. RESULTS: One hundred sixty-two controlled intervention studies with polyphenols were included, and mean recovery yield and correlations with the dose ingested were determined for 40 polyphenols. Polyphenols such as daidzein, genistein, glycitein, enterolactone, and hydroxytyrosol showed both a high recovery yield (12-37%) and a high correlation with the dose (Pearson's correlation coefficients: 0.67-0.87), which showed good sensitivity and robustness as biomarkers of intake throughout the different studies. Weaker recovery for anthocyanins (0.06-0.2%) and weaker correlations with dose [Pearson's correlation coefficients: 0.21-0.52 for hesperidin, naringenin, (-)-epicatechin, (-)-epigallocatechin, quercetin, and 3 microbial metabolites of isoflavones (dihydrodaidzein, equol, and O-desmethylangolensin)] suggest that they are currently less suitable as biomarkers of intake. CONCLUSIONS: These data confirm the value of certain urinary polyphenols as biomarkers of intake. A validation in populations is now needed to evaluate their specificity, sensitivity, and responsiveness to dose under free-living conditions.

Effects of isoflavones on breast density in pre- and post-menopausal women: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Isoflavones from soy and red clover exert modest hormonal effects in women, but the relevance to risk of breast cancer is unclear. The aim of this meta-analysis was to assess the effects of isoflavone-rich foods or supplements on a biomarker of breast cancer risk, women's mammographic density. METHODS: Electronic searches were performed on The Cochrane Library, Medline and EMBASE (to June 2009), and reference lists and trial investigators were consulted to identify further studies. Randomized controlled trials (RCTs) of isoflavone-rich foods or supplements versus placebo with a duration of at least 6 months were included in our analysis. Inclusion/exclusion, data extraction and validity assessment were carried out independently in duplicate, and meta-analysis used to pool study results. Subgrouping, sensitivity analysis, assessment of heterogeneity and funnel plots were used to interpret the results. RESULTS: Eight RCTs (1287 women) compared isoflavones with placebo for between 6 months and 3 years. Meta-analysis suggested no overall effect of dietary isoflavones on breast density in all women combined [mean difference (MD) 0.69%, 95% confidence interval (CI) -0.78 to 2.17] or post-menopausal women (MD -1.10%, 95% CI -3.22 to 1.03). However, there was a modest increase in mammographic density in premenopausal women (MD 1.83%, 95% CI 0.25-3.40) without heterogeneity but this effect was lost in one of three sensitivity analyses. CONCLUSIONS: Isoflavone intake does not alter breast density in post-menopausal women, but may cause a small increase in breast density in premenopausal women. Larger, long-term trials are required to determine if these small effects are clinically relevant.

The effects of oral iron supplementation on cognition in older children and adults: a systematic review and meta-analysis.

BACKGROUND: In observational studies anaemia and iron deficiency are associated with cognitive deficits, suggesting that iron supplementation may improve cognitive function. However, due to the potential for confounding by socio-economic status in observational studies, this needs to be verified in data from randomised controlled trials (RCTs). AIM: To assess whether iron supplementation improved cognitive domains: concentration, intelligence, memory, psychomotor skills and scholastic achievement. METHODOLOGY: Searches included MEDLINE, EMBASE, PsychINFO, Cochrane CENTRAL and bibliographies (to November 2008). Inclusion, data extraction and validity assessment were duplicated, and the meta-analysis used the standardised mean difference (SMD). Subgrouping, sensitivity analysis, assessment of publication bias and heterogeneity were employed. RESULTS: Fourteen RCTs of children aged 6+, adolescents and women were included; no RCTs in men or older people were found. Iron supplementation improved attention and concentration irrespective of baseline iron status (SMD 0.59, 95% CI 0.29 to 0.90) without heterogeneity. In anaemic groups supplementation improved intelligence quotient (IQ) by 2.5 points (95% CI 1.24 to 3.76), but had no effect on non-anaemic participants, or on memory, psychomotor skills or scholastic achievement. However, the funnel plot suggested modest publication bias. The limited number of included studies were generally small, short and methodologically weak. CONCLUSIONS: There was some evidence that iron supplementation improved attention, concentration and IQ, but this requires confirmation with well-powered, blinded, independently funded RCTs of at least one year's duration in different age groups including children, adolescents, adults and older people, and across all levels of baseline iron status.