Consumption of 100% Fruit Juice and Body Weight in Children and Adults: A Systematic Review and Meta-Analysis.

Importance: Concerns have been raised that frequent consumption of 100% fruit juice may promote weight gain. Current evidence on fruit juice and weight gain has yielded mixed findings from both observational studies and clinical trials. Objective: To synthesize the available evidence on 100% fruit juice consumption and body weight in children and adults. Data Sources: MEDLINE, Embase, and Cochrane databases were searched through May 18, 2023. Study Selection: Prospective cohort studies of at least 6 months and randomized clinical trials (RCTs) of at least 2 weeks assessing the association of 100% fruit juice with body weight change in children and adults were included. In the trials, fruit juices were compared with noncaloric controls. Data Extraction and Synthesis: Data were pooled using random-effects models and presented as ß coefficients with 95% CIs for cohort studies and mean differences (MDs) with 95% CIs for RCTs. Main Outcomes and Measures: Change in body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) was assessed in children and change in body weight in adults. Results: A total of 42 eligible studies were included in this analysis, including 17 among children (17 cohorts; 0 RCTs; 45 851 children; median [IQR] age, 8 [1-15] years) and 25 among adults (6 cohorts; 19 RCTs; 268 095 adults; median [IQR] age among cohort studies, 48 [41-61] years; median [IQR] age among RCTs, 42 [25-59]). Among cohort studies in children, each additional serving per day of 100% fruit juice was associated with a 0.03 (95% CI, 0.01-0.05) higher BMI change. Among cohort studies in adults, studies that did not adjust for energy showed greater body weight gain (0.21 kg; 95% CI, 0.15-0.27 kg) than studies that did adjust for energy intake (-0.08 kg; 95% CI, -0.11 to -0.05 kg; P for meta-regression <.001). RCTs in adults found no significant association of assignment to 100% fruit juice with body weight but the CI was wide (MD, -0.53 kg; 95% CI, -1.55 to 0.48 kg). Conclusion and Relevance: Based on the available evidence from prospective cohort studies, in this systematic review and meta-analysis, 1 serving per day of 100% fruit juice was associated with BMI gain among children. Findings in adults found a significant association among studies unadjusted for total energy, suggesting potential mediation by calories. Further trials of 100% fruit juice and body weight are desirable. Our findings support guidance to limit consumption of fruit juice to prevent intake of excess calories and weight gain.

Fructose-containing food sources and blood pressure: A systematic review and meta-analysis of controlled feeding trials.

Whether food source or energy mediates the effect of fructose-containing sugars on blood pressure (BP) is unclear. We conducted a systematic review and meta-analysis of the effect of different food sources of fructose-containing sugars at different levels of energy control on BP. We searched MEDLINE, Embase and the Cochrane Library through June 2021 for controlled trials ≥7-days. We prespecified 4 trial designs: substitution (energy matched substitution of sugars); addition (excess energy from sugars added); subtraction (excess energy from sugars subtracted); and ad libitum (energy from sugars freely replaced). Outcomes were systolic and diastolic BP. Independent reviewers extracted data. GRADE assessed the certainty of evidence. We included 93 reports (147 trial comparisons, N = 5,213) assessing 12 different food sources across 4 energy control levels in adults with and without hypertension or at risk for hypertension. Total fructose-containing sugars had no effect in substitution, subtraction, or ad libitum trials but decreased systolic and diastolic BP in addition trials (P<0.05). There was evidence of interaction/influence by food source: fruit and 100% fruit juice decreased and mixed sources (with sugar-sweetened beverages [SSBs]) increased BP in addition trials and the removal of SSBs (linear dose response gradient) and mixed sources (with SSBs) decreased BP in subtraction trials. The certainty of evidence was generally moderate. Food source and energy control appear to mediate the effect of fructose-containing sugars on BP. The evidence provides a good indication that fruit and 100% fruit juice at low doses (up to or less than the public health threshold of ~10% E) lead to small, but important reductions in BP, while the addition of excess energy of mixed sources (with SSBs) at high doses (up to 23%) leads to moderate increases and their removal or the removal of SSBs alone (up to ~20% E) leads to small, but important decreases in BP in adults with and without hypertension or at risk for hypertension. Trial registration: Clinicaltrials.gov: NCT02716870.

Lifestyle Factors Associated with Circulating Very Long-Chain Saturated Fatty Acids in Humans: A Systematic Review of Observational Studies.

Recent observational studies have documented inverse associations of circulating very long-chain saturated fatty acids (VLCSFAs), namely arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0), with cardiometabolic outcomes. In addition to their endogenous production, it has been suggested that dietary intake or an overall healthier lifestyle may influence VLCSFA concentrations; however, a systematic review of the modifiable lifestyle contributors to circulating VLCSFAs is lacking. Therefore, this review aimed to systematically assess the effects of diet, physical activity, and smoking on circulating VLCSFAs. Following registration on PROSPERO (International Prospective Register of Systematic Reviews) (ID: CRD42021233550), a systematic search of observational studies was conducted in MEDLINE, EMBASE, and The Cochrane databases up to February 2022. A total of 12 studies consisting of mostly cross-sectional analyses were included in this review. The majority of the studies documented the associations of dietary intake with total plasma or red blood cell VLCSFAs, in which a range of macronutrients and food groups were examined. Two cross-sectional analyses showed a consistent positive association between total fat and peanut intake with 22:0 and 24:0 and an inverse association between alcohol intake and 20:0 and 22:0. Furthermore, a moderate positive association between physical activity and 22:0 and 24:0 was observed. Lastly, there were conflicting results on the effects of smoking on VLCSFA. Although most studies had a low risk of bias; the findings of this review are limited by the bi-variate analyses presented in the majority of the included studies, therefore, the impact of confounding is unclear. In conclusion, although the current observational literature examining lifestyle determinants of VLCSFAs is limited, existing evidence suggests that circulating 22:0 and 24:0 may be influenced by higher total and saturated fat consumption and nut intake.

Combination of Multiple Low-Risk Lifestyle Behaviors and Incident Type 2 Diabetes: A Systematic Review and Dose-Response Meta-analysis of Prospective Cohort Studies.

OBJECTIVE: Combined low-risk lifestyle behaviors (LRLBs) have been associated with a reduction in type 2 diabetes risk. This relationship has not been systematically quantified. RESEARCH DESIGN AND METHODS: A systematic review and meta-analysis was conducted to assess the association of combined LRLBs with type 2 diabetes. Databases were searched up to September 2022. Prospective cohort studies reporting the association between a minimum of three combined LRLBs (including healthy diet) with incident type 2 diabetes were included. Independent reviewers extracted data and assessed study quality. Risk estimates of extreme comparisons were pooled using a random-effects model. Global dose-response meta-analysis (DRM) for maximum adherence was estimated using a one-stage linear mixed model. The certainty of the evidence was assessed using GRADE (Grading of Recommendations, Assessment, Development and Evaluations). RESULTS: Thirty cohort comparisons (n = 1,693,753) involving 75,669 incident type 2 diabetes cases were included. LRLBs, with author-defined ranges, were healthy body weight, healthy diet, regular exercise, smoking abstinence or cessation, and light alcohol consumption. LRLBs were associated with 80% lower risk of type 2 diabetes (relative risk [RR] 0.20; 95% CI 0.17-0.23), comparing the highest with lowest adherence. Global DRM for maximum adherence to all five LRLBs reached 85% protection (RR 0.15; 95% CI 0.12-0.18). The overall certainty of the evidence was graded as high. CONCLUSIONS: There is a very good indication that a combination of LRLBs that includes maintaining a healthy bodyweight, healthy diet, regular exercise, smoking abstinence or cessation, and light alcohol consumption is associated with a lower risk of incident type 2 diabetes.

Sugar-sweetened beverage consumption and weight gain in children and adults: a systematic review and meta-analysis of prospective cohort studies and randomized controlled trials.

BACKGROUND: Sugar-sweetened beverages (SSBs) have been implicated in fueling the obesity epidemic. OBJECTIVES: This study aimed to update a synthesis of the evidence on SSBs and weight gain in children and adults. METHODS: MEDLINE, Embase, and Cochrane databases were searched through September 8, 2022, for prospective cohort studies and randomized controlled trials (RCTs) that evaluated intake of SSBs in relation to BMI and body weight in children and adults, respectively. Eligible interventions were compared against a noncaloric control. Study-level estimates were pooled using random-effects meta-analysis and presented as ß-coefficients with 95% CIs for cohorts and weighted mean differences (MDs) with 95% CIs for RCTs. RESULTS: We identified 85 articles including 48 in children (40 cohorts, n = 91,713; 8 RCTs, n = 2783) and 37 in adults (21 cohorts, n = 448,661; 16 RCTs, n = 1343). Among cohort studies, each serving/day increase in SSB intake was associated with a 0.07-kg/m2 (95% CI: 0.04 kg/m2, 0.10 kg/m2) higher BMI in children and a 0.42-kg (95% CI: 0.26 kg, 0.58 kg) higher body weight in adults. RCTs in children indicated less BMI gain with SSB reduction interventions compared with control (MD: -0.21 kg/m2; 95% CI: -0.40 kg/m2, -0.01 kg/m2). In adults, randomization to addition of SSBs to the diet led to greater body weight gain (MD: 0.83 kg; 95% CI: 0.47 kg, 1.19 kg), and subtraction of SSBs led to weight loss (MD: -0.49 kg; 95% CI: -0.66 kg, -0.32 kg) compared with the control groups. A positive linear dose-response association between SSB consumption and weight gain was found in all outcomes assessed. CONCLUSIONS: Our updated systematic review and meta-analysis expands on prior evidence to confirm that SSB consumption promotes higher BMI and body weight in both children and adults, underscoring the importance of dietary guidance and public policy strategies to limit intake. This meta-analysis was registered at the International Prospective Register of Systematic Reviews as CRD42020209915.

Nordic dietary patterns and cardiometabolic outcomes: a systematic review and meta-analysis of prospective cohort studies and randomised controlled trials.

AIMS/HYPOTHESIS: Nordic dietary patterns that are high in healthy traditional Nordic foods may have a role in the prevention and management of diabetes. To inform the update of the EASD clinical practice guidelines for nutrition therapy, we conducted a systematic review and meta-analysis of Nordic dietary patterns and cardiometabolic outcomes. METHODS: We searched MEDLINE, EMBASE and The Cochrane Library from inception to 9 March 2021. We included prospective cohort studies and RCTs with a follow-up of ≥1 year and ≥3 weeks, respectively. Two independent reviewers extracted relevant data and assessed the risk of bias (Newcastle-Ottawa Scale and Cochrane risk of bias tool). The primary outcome was total CVD incidence in the prospective cohort studies and LDL-cholesterol in the RCTs. Secondary outcomes in the prospective cohort studies were CVD mortality, CHD incidence and mortality, stroke incidence and mortality, and type 2 diabetes incidence; in the RCTs, secondary outcomes were other established lipid targets (non-HDL-cholesterol, apolipoprotein B, HDL-cholesterol, triglycerides), markers of glycaemic control (HbA1c, fasting glucose, fasting insulin), adiposity (body weight, BMI, waist circumference) and inflammation (C-reactive protein), and blood pressure (systolic and diastolic blood pressure). The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of the evidence. RESULTS: We included 15 unique prospective cohort studies (n=1,057,176, with 41,708 cardiovascular events and 13,121 diabetes cases) of people with diabetes for the assessment of cardiovascular outcomes or people without diabetes for the assessment of diabetes incidence, and six RCTs (n=717) in people with one or more risk factor for diabetes. In the prospective cohort studies, higher adherence to Nordic dietary patterns was associated with 'small important' reductions in the primary outcome, total CVD incidence (RR for highest vs lowest adherence: 0.93 [95% CI 0.88, 0.99], p=0.01; substantial heterogeneity: I2=88%, pQ<0.001), and similar or greater reductions in the secondary outcomes of CVD mortality and incidence of CHD, stroke and type 2 diabetes (p<0.05). Inverse dose-response gradients were seen for total CVD incidence, CVD mortality and incidence of CHD, stroke and type 2 diabetes (p<0.05). No studies assessed CHD or stroke mortality. In the RCTs, there were small important reductions in LDL-cholesterol (mean difference [MD] -0.26 mmol/l [95% CI -0.52, -0.00], pMD=0.05; substantial heterogeneity: I2=89%, pQ<0.01), and 'small important' or greater reductions in the secondary outcomes of non-HDL-cholesterol, apolipoprotein B, insulin, body weight, BMI and systolic blood pressure (p<0.05). For the other outcomes there were 'trivial' reductions or no effect. The certainty of the evidence was low for total CVD incidence and LDL-cholesterol; moderate to high for CVD mortality, established lipid targets, adiposity markers, glycaemic control, blood pressure and inflammation; and low for all other outcomes, with evidence being downgraded mainly because of imprecision and inconsistency. CONCLUSIONS/INTERPRETATION: Adherence to Nordic dietary patterns is associated with generally small important reductions in the risk of major CVD outcomes and diabetes, which are supported by similar reductions in LDL-cholesterol and other intermediate cardiometabolic risk factors. The available evidence provides a generally good indication of the likely benefits of Nordic dietary patterns in people with or at risk for diabetes. REGISTRATION: ClinicalTrials.gov NCT04094194. FUNDING: Diabetes and Nutrition Study Group of the EASD Clinical Practice.

Neither soyfoods nor isoflavones warrant classification as endocrine disruptors: a technical review of the observational and clinical data.

Soybeans are a rich source of isoflavones, which are classified as phytoestrogens. Despite numerous proposed benefits, isoflavones are often classified as endocrine disruptors, based primarily on animal studies. However, there are ample human data regarding the health effects of isoflavones. We conducted a technical review, systematically searching Medline, EMBASE, and the Cochrane Library (from inception through January 2021). We included clinical studies, observational studies, and systematic reviews and meta-analyses (SRMA) that examined the relationship between soy and/or isoflavone intake and endocrine-related endpoints. 417 reports (229 observational studies, 157 clinical studies and 32 SRMAs) met our eligibility criteria. The available evidence indicates that isoflavone intake does not adversely affect thyroid function. Adverse effects are also not seen on breast or endometrial tissue or estrogen levels in women, or testosterone or estrogen levels, or sperm or semen parameters in men. Although menstrual cycle length may be slightly increased, ovulation is not prevented. Limited insight could be gained about possible impacts of in utero isoflavone exposure, but the existing data are reassuring. Adverse effects of isoflavone intake were not identified in children, but limited research has been conducted. After extensive review, the evidence does not support classifying isoflavones as endocrine disruptors.

Comparing the Effects of Docosahexaenoic and Eicosapentaenoic Acids on Inflammation Markers Using Pairwise and Network Meta-Analyses of Randomized Controlled Trials.

Recent data from randomized clinical trials (RCTs) suggest that DHA may have stronger anti-inflammatory effects than EPA. This body of evidence has not yet been quantitatively reviewed. The aim of this study was to compare the effect of DHA and EPA on several markers of systemic inflammation by pairwise and network meta-analyses of RCTs. MEDLINE, EMBASE, and The Cochrane Library were searched through to September 2019. We included RCTs of ≥7 d on adults regardless of health status that directly compared the effects of DHA with EPA and RCTs of indirect comparisons, in which the effects of DHA or EPA were compared individually to a control fatty acid. Differences in circulating concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and adiponectin were the primary outcome measures. Data were pooled by pairwise and network meta-analysis and expressed as mean differences (MDs) with 95% CIs. Heterogeneity was assessed (Cochran Q statistic) and quantified (I2 statistic) in the pairwise meta-analysis. Inconsistency and transitivity were evaluated in the network meta-analysis. The certainty of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Eligibility criteria were met by 5 RCTs (N = 411) for the pairwise meta-analysis and 20 RCTs (N = 1231) for the network meta-analysis. In the pairwise meta-analysis, DHA and EPA had similar effects on plasma CRP [MDDHA versus EPA = 0.14 mg/L (95% CI: -0.57, 0.85); I2 = 61%], IL-6 [MDDHA versus EPA = 0.10 pg/mL (-0.15, 0.34); I2 = 40%], and TNF-α [MDDHA versus EPA = -0.10 pg/mL (-0.37, 0.18); I2 = 40%]. In the network meta-analysis, the effects of DHA and EPA on plasma CRP [MDDHA versus EPA = -0.33 mg/L (-0.75, 0.10)], IL-6 [MDDHA versus EPA = 0.09 pg/mL (-0.12, 0.30)], and TNF-α [MDDHA versus EPA = -0.02 pg/mL (-0.25, 0.20)] were also similar. DHA and EPA had similar effects on plasma adiponectin in the network meta-analysis. Results from pairwise and network meta-analyses suggest that supplementation with either DHA or EPA does not differentially modify systemic markers of subclinical inflammation.

Repeated administration of inorganic nitrate on blood pressure and arterial stiffness: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: We aim to synthesize effects of repeated administration (≥3 days) of inorganic nitrate on blood pressure and arterial stiffness measures. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials with at least 3 days treatment of inorganic nitrate on blood pressure and arterial stiffness in individuals with or without elevated cardiovascular disease risk. MEDLINE, EMBASE and the Cochrane Library were searched through 2 July 2019. Two independent reviewers extracted relevant study data. Data were pooled using the generic inverse variance method with random-effects model, and expressed as mean differences with 95% confidence intervals. Certainty in the evidence was assessed using GRADE. RESULTS: Forty-seven trials were included (n = 1101). Administration of inorganic nitrate significantly lowered SBP [mean difference: -2.91 mmHg, 95% confidence interval (95% CI): -3.92 to -1.89, I = 76%], DBP (mean difference: -1.45 mmHg, 95% CI: -2.22 to -0.68, I = 78%], central SBP (mean difference: -1.56 mmHg, 95% CI: -2.62 to -0.50, I = 30%) and central DBP (mean difference: -1.99 mmHg, 95% CI: -2.37 to -1.60, I = 0%). There was no effect on 24-h blood pressure, augmentation index or pulse wave velocity. Certainty in the evidence was graded moderate for central blood pressure, pulse wave velocity and low for peripheral blood pressure, 24-h blood pressure and augmentation index. CONCLUSION: Repeated administration (≥3 days) of inorganic nitrate lower peripheral and central blood pressure. Results appear to be driven by beneficial effects in healthy and hypertensive individuals. More studies are required to increase certainty in the evidence.

Effect of fructose and its epimers on postprandial carbohydrate metabolism: A systematic review and meta-analysis.

AIMS: To synthesize the evidence of the effect of small doses (≤30-g/meal) of fructose and its epimers (allulose, tagatose, and sorbose) on the postprandial glucose and insulin response to carbohydrate-containing meals. METHODS: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched through to April 9, 2019. We included randomized (RCTs) and non-randomized acute, single-meal, controlled feeding trials that added ≤30-g of fructose or its epimers either prior to or with a carbohydrate-containing meal compared with the same meal alone. Outcomes included the incremental area under the curve (iAUC) for glucose and insulin, the Matsuda Insulin Sensitivity Index, and the Early Insulin Secretion Index. Data were expressed as ratio of means (RoM) with 95% CIs and pooled using the inverse variance method. The overall certainty of the evidence was evaluated using GRADE. RESULTS: Forty trial comparisons (n = 400) were included (none for sorbose). Allulose significantly reduced the postprandial iAUC glucose response by 10% (0.90 [0.84 to 0.96], P < 0.01). Tagatose significantly reduced the postprandial iAUC insulin response by 25% (0.75 [0.62 to 0.91], P < 0.01) and showed a non-significant 3% reduction in the postprandial iAUC glucose response (0.97 [0.94 to 1.00], P = 0.07). There was no effect of fructose on any outcome. The certainty of the evidence was graded as low to moderate for fructose, moderate for allulose, and low for tagatose. CONCLUSIONS: Small doses of allulose and tagatose, but not fructose, lead to modest improvements on postprandial glucose and insulin regulation. There is a need for long-term RCTs to confirm the sustainability of these improvements.

Relation of Total Sugars, Sucrose, Fructose, and Added Sugars With the Risk of Cardiovascular Disease: A Systematic Review and Dose-Response Meta-analysis of Prospective Cohort Studies.

OBJECTIVE: To determine the association of total and added fructose-containing sugars on cardiovascular (CVD) incidence and mortality. METHODS: MEDLINE, EMBASE and Cochrane Library were searched from January 1, 1980, to July 31, 2018. Prospective cohort studies assessing the association of reported intakes of total, sucrose, fructose and added sugars with CVD incidence and mortality in individuals free from disease at baseline were included. Risk estimates were pooled using the inverse variance method, and dose-response analysis was modeled. RESULTS: Eligibility criteria were met by 24 prospective cohort comparisons (624,128 unique individuals; 11,856 CVD incidence cases and 12,224 CVD mortality cases). Total sugars, sucrose, and fructose were not associated with CVD incidence. Total sugars (risk ratio, 1.09 [95% confidence interval, 1.02 to 1.17]) and fructose (1.08 [1.01 to 1.15]) showed a harmful association for CVD mortality, there was no association for added sugars and a beneficial association for sucrose (0.94 [0.89 to 0.99]). Dose-response analyses showed a beneficial linear dose-response gradient for sucrose and nonlinear dose-response thresholds for harm for total sugars (133 grams, 26% energy), fructose (58 grams, 11% energy) and added sugars (65 grams, 13% energy) in relation to CVD mortality (P<.05). The certainty of the evidence using GRADE was very low for CVD incidence and low for CVD mortality for all sugar types. CONCLUSION: Current evidence supports a threshold of harm for intakes of total sugars, added sugars, and fructose at higher exposures and lack of harm for sucrose independent of food form for CVD mortality. Further research of different food sources of sugars is needed to define better the relationship between sugars and CVD. REGISTRATION: clinicaltrials.gov, NCT01608620.

Associations between Dietary Pulses Alone or with Other Legumes and Cardiometabolic Disease Outcomes: An Umbrella Review and Updated Systematic Review and Meta-analysis of Prospective Cohort Studies.

To update the European Association for the Study of Diabetes clinical practice guidelines for nutrition therapy, we conducted an umbrella review and updated systematic review and meta-analysis (SRMA) of prospective cohort studies of the association between dietary pulses with or without other legumes and cardiometabolic disease outcomes. We searched the PubMed, MEDLINE, EMBASE, and Cochrane databases through March 2019. We included the most recent SRMAs of prospective cohort studies and new prospective cohort studies published after the census dates of the included SRMAs assessing the relation between dietary pulses with or without other legumes and incidence and mortality of cardiovascular diseases (CVDs) [including coronary heart disease (CHD), myocardial infarction (MI), and stroke], diabetes, hypertension, and/or obesity. Two independent reviewers extracted data and assessed risk of bias. Risk estimates were pooled using the generic inverse variance method and expressed as risk ratios (RRs) with 95% CIs. The overall certainty of the evidence was assessed using the GRADE approach. Six SRMAs were identified and updated to include 28 unique prospective cohort studies with the following number of cases for each outcome: CVD incidence, 10,261; CVD mortality, 16,168; CHD incidence, 7786; CHD mortality, 3331; MI incidence, 2585; stroke incidence, 8570; stroke mortality, 2384; diabetes incidence, 10,457; hypertension incidence, 83,284; obesity incidence, 8125. Comparing the highest with the lowest level of intake, dietary pulses with or without other legumes were associated with significant decreases in CVD (RR: 0.92; 95% CI: 0.85, 0.99), CHD (RR: 0.90; 95% CI: 0.83, 0.99), hypertension (RR: 0.91; 95% CI: 0.86, 0.97), and obesity (RR: 0.87; 95% CI: 0.81, 0.94) incidence. There was no association with MI, stroke, and diabetes incidence or CVD, CHD, and stroke mortality. The overall certainty of the evidence was graded as "low" for CVD incidence and "very low" for all other outcomes. Current evidence shows that dietary pulses with or without other legumes are associated with reduced CVD incidence with low certainty and reduced CHD, hypertension, and obesity incidence with very low certainty. More research is needed to improve our estimates. This trial was registered at clinicaltrials.gov as NCT03555734.

Effect of vegetarian dietary patterns on cardiometabolic risk factors in diabetes: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND & AIMS: To update the European Association for the Study of Diabetes (EASD) clinical practice guidelines for nutrition therapy, we conducted a systematic review and meta-analysis of randomized controlled trials to summarize the evidence for the effect of vegetarian dietary patterns on glycemic control and other established cardiometabolic risk factors in individuals with diabetes. METHODS: We searched MEDLINE, EMBASE, and Cochrane databases through February 26, 2018 for randomized controlled trials ≥3 weeks assessing the effect of vegetarian dietary patterns in individuals with diabetes. The primary outcome was HbA1c. Secondary outcomes included other markers of glycemic control, blood lipids, body weight/adiposity, and blood pressure. Two independent reviewers extracted data and assessed risk of bias. Data were pooled by the generic inverse variance method and expressed as mean differences (MD) with 95% CIs. Heterogeneity was assessed (Cochran Q statistic) and quantified (I2 statistic). The overall certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. RESULTS: Nine trials (n = 664 participants) met the eligibility criteria. Vegetarian dietary patterns significantly lowered HbA1c (MD = -0.29% [95% CI: -0.45, -0.12%]), fasting glucose (MD = -0.56 mmol/L [95% CI: -0.99, -0.13 mmol/L]), LDL-C (MD = -0.12 mmol/L [95% CI: -0.20, -0.04 mmol/L]), non-HDL-C (MD = -0.13 mmol/L [95% CI: -0.26, -0.01 mmol/L]), body weight (MD = -2.15 kg [95% CI: -2.95, -1.34 kg]), BMI (MD = -0.74 kg/m2 [95% CI: -1.09, -0.39 kg/m2]) and waist circumference (MD = -2.86 cm [95% CI: -3.76, -1.96 cm]). There was no significant effect on fasting insulin, HDL-C, triglycerides or blood pressure. The overall certainty of evidence was moderate but was low for fasting insulin, triglycerides and waist circumference. CONCLUSION: Vegetarian dietary patterns improve glycemic control, LDL-C, non-HDL-C, and body weight/adiposity in individuals with diabetes, supporting their inclusion for diabetes management. More research is needed to improve our confidence in the estimates. CLINICALTRIALS. GOV IDENTIFIER: NCT02600377.

Portfolio Dietary Pattern and Cardiovascular Disease: A Systematic Review and Meta-analysis of Controlled Trials.

BACKGROUND: The evidence for the Portfolio dietary pattern, a plant-based dietary pattern that combines recognized cholesterol-lowering foods (nuts, plant protein, viscous fibre, plant sterols), has not been summarized. OBJECTIVE: To update the European Association for the Study of Diabetes clinical practice guidelines for nutrition therapy, we conducted a systematic review and meta-analysis of controlled trials using GRADE of the effect of the Portfolio dietary pattern on the primary therapeutic lipid target for cardiovascular disease prevention, low-density lipoprotein cholesterol (LDL-C), and other established cardiometabolic risk factors. METHODS: We searched MEDLINE, EMBASE, and The Cochrane Library through April 19, 2018. We included controlled trials ≥ 3-weeks assessing the effect of the Portfolio dietary pattern on cardiometabolic risk factors compared with an energy-matched control diet free of Portfolio dietary pattern components. Two independent reviewers extracted data and assessed risk of bias. The primary outcome was LDL-C. Data were pooled using the generic inverse-variance method and expressed as mean differences (MDs) with 95% confidence intervals (CIs). Heterogeneity was assessed (Cochran Q statistic) and quantified (I2-statistic). GRADE assessed the certainty of the evidence. RESULTS: Eligibility criteria were met by 7 trial comparisons in 439 participants with hyperlipidemia, in which the Portfolio dietary pattern was given on a background of a National Cholesterol Education Program (NCEP) Step II diet. The combination of a portfolio dietary pattern and NCEP Step II diet significantly reduced the primary outcome LDL-C by ~17% (MD, -0.73 mmol/L, [95% CI, -0.89 to -0.56 mmol/L]) as well as non-high-density lipoprotein cholesterol, apolipoprotein B, total cholesterol, triglycerides, systolic and diastolic blood pressure, C-reactive protein, and estimated 10-year coronary heart disease (CHD) risk, compared with an NCEP Step 2 diet alone (p < 0.05). There was no effect on high-density lipoprotein cholesterol or body weight. The certainty of the evidence was high for LDL-cholesterol and most lipid outcomes and moderate for all others outcomes. CONCLUSIONS: Current evidence demonstrates that the Portfolio dietary pattern leads to clinically meaningful improvements in LDL-C as well as other established cardiometabolic risk factors and estimated 10-year CHD risk.

Relation of total sugars, fructose and sucrose with incident type 2 diabetes: a systematic review and meta-analysis of prospective cohort studies.

BACKGROUND: Sugar-sweetened beverages are associated with type 2 diabetes. To assess whether this association holds for the fructose-containing sugars they contain, we conducted a systematic review and meta-analysis of prospective cohort studies. METHODS: We searched MEDLINE, Embase, CINAHL and the Cochrane Library (through June 2016). We included prospective cohort studies that assessed the relation of fructose-containing sugars with incident type 2 diabetes. Two independent reviewers extracted relevant data and assessed risk of bias. We pooled risk ratios (RRs) using random effects meta-analyses. The overall quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. RESULTS: Fiffeen prospective cohort studies (251 261 unique participants, 16 416 cases) met the eligibility criteria, comparing the highest intake (median 137, 35.2 and 78 g/d) with the lowest intake (median 65, 9.7 and 25.8 g/d) of total sugars, fructose and sucrose, respectively. Although there was no association of total sugars (RR 0.91, 95% confidence interval [CI] 0.76-1.09) or fructose (RR 1.04, 95% CI 0.84-1.29) with type 2 diabetes, sucrose was associated with a decreased risk of type 2 diabetes (RR 0.89, 95% CI 0.80-0.98). Our confidence in the estimates was limited by evidence of serious inconsistency between studies for total sugars and fructose, and serious imprecision in the pooled estimates for all 3 sugar categories. INTERPRETATION: Current evidence does not allow us to conclude that fructose-containing sugars independent of food form are associated with increased risk of type 2 diabetes. Further research is likely to affect our estimates. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT01608620.

The effect of alpha-linolenic acid on glycemic control in individuals with type 2 diabetes: A systematic review and meta-analysis of randomized controlled clinical trials.

BACKGROUND: Polyunsaturated fats (PUFAs) have been shown to reduce type 2 diabetes (T2DM) risk and improve insulin responsiveness in T2DM subjects, but whether the plant sources of omega-3 PUFA (alpha-linolenic acid [ALA]) have an effect on glycemic control requires further investigation. METHODS: The parameters of interest were glycated hemoglobin (HbA1c), fasting blood glucose (FBG), fasting blood insulin (FBI), homeostatic model assessment for insulin resistance (HOMA-IR), fructosamine, and glycated albumin. A comprehensive search was conducted with MEDLINE, Embase, CINAHL, and Cochrane. Eligible studies included randomized controlled trials (RCTs) ≥1 month in duration that compared diets enriched in ALA with usual diets on glycemic parameters. For each study, the risk of bias as well as the study quality was assessed. Using the statistical software RevMan (v5.3), data were pooled using the generic inverse method with random effects model, and final results were expressed as mean differences (MD) with 95% confidence intervals (CI). Heterogeneity was assessed by the Cochran Q statistic and quantified by the I statistic. RESULTS: A total of 8 trials (N = 212) were included in the meta-analysis. Compared to a control diet, a median dose of 4.4 g/day of ALA intake for a median duration of 3 months did not affect HbA1c (%) (MD = -.01; [95%: -.32, .31], P = .96). A median ALA dose of 5.4 g/day did not lower FBG (MD = .07; [95% CI: -.61, .76], P = .84) or FBI (MD = 7.03, [95% CI: -5.84, 19.89], P = .28). Summary effect estimates were generally compromised by considerable and unexplained heterogeneity (I ≥75%). In the subgroup analysis of continuous predictors, a reduction in HbA1c (%) and FBG (mmol/L) was significantly associated with an increased intake of ALA. Further adjustment for Publication Bias using Duval and Tweedie's trim-and-fill analysis provided an adjusted, significant MD of -.25 (95% CI: -.38, -.12; P <.001) for HbA1c (%). CONCLUSIONS: ALA-enriched diets did not affect HbA1c, FBG, or FBI. The scarce number of existing RCTs and the presence of heterogeneity in our meta-analysis limit the ability to make firm conclusions about ALA in T2DM management. The potential for ALA to have dose-dependent effects warrants further research in this area.

Effect of dietary pulse intake on established therapeutic lipid targets for cardiovascular risk reduction: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Evidence from controlled trials encourages the intake of dietary pulses (beans, chickpeas, lentils and peas) as a method of improving dyslipidemia, but heart health guidelines have stopped short of ascribing specific benefits to this type of intervention or have graded the beneficial evidence as low. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effect of dietary pulse intake on established therapeutic lipid targets for cardiovascular risk reduction. METHODS: We searched electronic databases and bibliographies of selected trials for relevant articles published through Feb. 5, 2014. We included RCTs of at least 3 weeks' duration that compared a diet emphasizing dietary pulse intake with an isocaloric diet that did not include dietary pulses. The lipid targets investigated were low-density lipoprotein (LDL) cholesterol, apolipoprotein B and non-high-density lipoprotein (non-HDL) cholesterol. We pooled data using a random-effects model. RESULTS: We identified 26 RCTs (n = 1037) that satisfied the inclusion criteria. Diets emphasizing dietary pulse intake at a median dose of 130 g/d (about 1 serving daily) significantly lowered LDL cholesterol levels compared with the control diets (mean difference -0.17 mmol/L, 95% confidence interval -0.25 to -0.09 mmol/L). Treatment effects on apolipoprotein B and non-HDL cholesterol were not observed. INTERPRETATION: Our findings suggest that dietary pulse intake significantly reduces LDL cholesterol levels. Trials of longer duration and higher quality are needed to verify these results. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT01594567.