Weight management using meal replacements and cardiometabolic risk reduction in individuals with pre-diabetes and features of metabolic syndrome: A systematic review and meta-analysis of randomized controlled trials.

This review synthesized the evidence from randomized controlled trials comparing the effect of meal replacements (MRs) as part of a weight loss intervention with conventional food-based weight loss diets on cardiometabolic risk in individuals with pre-diabetes and features of metabolic syndrome. MEDLINE, EMBASE, and Cochrane Library were searched through January 16, 2024. Data were pooled using the generic inverse variance method and expressed as mean difference [95% confidence intervals]. The overall certainty of the evidence was assessed using GRADE. Ten trials (n = 1254) met the eligibility criteria. MRs led to greater reductions in body weight (-1.38 kg [-1.81, -0.95]), body mass index (BMI, -0.56 kg/m2 [-0.78, -0.34]), waist circumference (-1.17 cm [-1.93, -0.41]), HbA1c (-0.11% [-0.22, 0.00]), LDL-c (-0.18 mmol/L [-0.28, -0.08]), non-HDL-c (-0.17 mmol/L [-0.33, -0.01]), and systolic blood pressure (-2.22 mmHg [-4.20, -0.23]). The overall certainty of the evidence was low to moderate owing to imprecision and/or inconsistency. The available evidence suggests that incorporating MRs into a weight loss intervention leads to small important reductions in body weight, BMI, LDL-c, non-HDL-c, and systolic blood pressure, and trivial reductions in waist circumference and HbA1c, beyond that seen with conventional food-based weight loss diets.

Rationale, Design and Participants Baseline Characteristics of a Crossover Randomized Controlled Trial of the Effect of Replacing SSBs with NSBs versus Water on Glucose Tolerance, Gut Microbiome and Cardiometabolic Risk in Overweight or Obese Adult SSB Consumer: Strategies to Oppose SUGARS with Non-Nutritive Sweeteners or Water (STOP Sugars NOW) Trial and Ectopic Fat Sub-Study.

BACKGROUND: Health authorities are near universal in their recommendation to replace sugar-sweetened beverages (SSBs) with water. Non-nutritive sweetened beverages (NSBs) are not as widely recommended as a replacement strategy due to a lack of established benefits and concerns they may induce glucose intolerance through changes in the gut microbiome. The STOP Sugars NOW trial aims to assess the effect of the substitution of NSBs (the "intended substitution") versus water (the "standard of care substitution") for SSBs on glucose tolerance and microbiota diversity. DESIGN AND METHODS: The STOP Sugars NOW trial (NCT03543644) is a pragmatic, "head-to-head", open-label, crossover, randomized controlled trial conducted in an outpatient setting. Participants were overweight or obese adults with a high waist circumference who regularly consumed ≥1 SSBs daily. Each participant completed three 4-week treatment phases (usual SSBs, matched NSBs, or water) in random order, which were separated by ≥4-week washout. Blocked randomization was performed centrally by computer with allocation concealment. Outcome assessment was blinded; however, blinding of participants and trial personnel was not possible. The two primary outcomes are oral glucose tolerance (incremental area under the curve) and gut microbiota beta-diversity (weighted UniFrac distance). Secondary outcomes include related markers of adiposity and glucose and insulin regulation. Adherence was assessed by objective biomarkers of added sugars and non-nutritive sweeteners and self-report intake. A subset of participants was included in an Ectopic Fat sub-study in which the primary outcome is intrahepatocellular lipid (IHCL) by 1H-MRS. Analyses will be according to the intention to treat principle. BASELINE RESULTS: Recruitment began on 1 June 2018, and the last participant completed the trial on 15 October 2020. We screened 1086 participants, of whom 80 were enrolled and randomized in the main trial and 32 of these were enrolled and randomized in the Ectopic Fat sub-study. The participants were predominantly middle-aged (mean age 41.8 ± SD 13.0 y) and had obesity (BMI of 33.7 ± 6.8 kg/m2) with a near equal ratio of female: male (51%:49%). The average baseline SSB intake was 1.9 servings/day. SSBs were replaced with matched NSB brands, sweetened with either a blend of aspartame and acesulfame-potassium (95%) or sucralose (5%). CONCLUSIONS: Baseline characteristics for both the main and Ectopic Fat sub-study meet our inclusion criteria and represent a group with overweight or obesity, with characteristics putting them at risk for type 2 diabetes. Findings will be published in peer-reviewed open-access medical journals and provide high-level evidence to inform clinical practice guidelines and public health policy for the use NSBs in sugars reduction strategies. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03543644.

Important food sources of fructose-containing sugars and adiposity: A systematic review and meta-analysis of controlled feeding trials.

BACKGROUND: Sugar-sweetened beverages (SSBs) providing excess energy increase adiposity. The effect of other food sources of sugars at different energy control levels is unclear. OBJECTIVES: To determine the effect of food sources of fructose-containing sugars by energy control on adiposity. METHODS: In this systematic review and meta-analysis, MEDLINE, Embase, and Cochrane Library were searched through April 2022 for controlled trials ≥2 wk. We prespecified 4 trial designs by energy control: substitution (energy-matched replacement of sugars), addition (energy from sugars added), subtraction (energy from sugars subtracted), and ad libitum (energy from sugars freely replaced). Independent authors extracted data. The primary outcome was body weight. Secondary outcomes included other adiposity measures. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to assess the certainty of evidence. RESULTS: We included 169 trials (255 trial comparisons, n = 10,357) assessing 14 food sources at 4 energy control levels over a median 12 wk. Total fructose-containing sugars increased body weight (MD: 0.28 kg; 95% CI: 0.06, 0.50 kg; PMD = 0.011) in addition trials and decreased body weight (MD: -0.96 kg; 95% CI: -1.78, -0.14 kg; PMD = 0.022) in subtraction trials with no effect in substitution or ad libitum trials. There was interaction/influence by food sources on body weight: substitution trials [fruits decreased; added nutritive sweeteners and mixed sources (with SSBs) increased]; addition trials [dried fruits, honey, fruits (≤10%E), and 100% fruit juice (≤10%E) decreased; SSBs, fruit drink, and mixed sources (with SSBs) increased]; subtraction trials [removal of mixed sources (with SSBs) decreased]; and ad libitum trials [mixed sources (with/without SSBs) increased]. GRADE scores were generally moderate. Results were similar across secondary outcomes. CONCLUSIONS: Energy control and food sources mediate the effect of fructose-containing sugars on adiposity. The evidence provides a good indication that excess energy from sugars (particularly SSBs at high doses ≥20%E or 100 g/d) increase adiposity, whereas their removal decrease adiposity. Most other food sources had no effect, with some showing decreases (particularly fruits at lower doses ≤10%E or 50 g/d). This trial was registered at clinicaltrials.gov as NCT02558920 (https://clinicaltrials.gov/ct2/show/NCT02558920).

Association of branched chain fatty acids with cardiometabolic disorders in humans: a systematic review.

CONTEXT: Despite advances in treatments for cardiometabolic disorders such as type 2 diabetes mellitus and obesity, the increasing frequency of these conditions is of major clinical and public health concern. Therefore, primary prevention including diet and lifestyle approaches continues to play a key role in risk reduction. Meta-analyses of prospective cohort studies have documented inverse associations of dairy consumption with the incidence of different cardiometabolic disorders. Dairy is the largest dietary contributor of branched chain fatty acids (BCFAs), which have been suggested to not only serve as biomarkers of dairy consumption but may also have bioactive properties contributing to reducing the risk of cardiometabolic outcomes. To date, however, the literature on this topic has not been systematically reviewed. OBJECTIVE: The aim here was to report the results of a systematic review of the association of BCFAs with cardiometabolic disorders in humans. DATA SOURCES: Search terms were developed and run through the Ovid MEDLINE, Ovid Embase, and the Cochrane Library databases. DATA EXTRACTION: Articles were selected on the basis of prespecified inclusion criteria and assessed for risk of bias by independent reviewers. RESULTS: Four studies (n = 2 cross sectional; n = 1 randomized feeding trial and n = 1 pre-post study) were identified. Two studies reported significant inverse associations between serum BCFAs and insulin resistance, triglycerides and/or body mass index. One study identified an inverse association between adipose tissue monomethyl BCFAs and skeletal muscle insulin resistance. In contrast, the randomized feeding trial reported no significant differences to stool BCFA concentrations or body mass index in obese participants following assignment to fruit-vegetable or whole-grain diet groups compared with a refined-grain control group. CONCLUSIONS: Current evidence suggests beneficial associations of circulating BCFAs with cardiometabolic risk phenotypes, although data in human participants are limited, indicating that additional research is required. PROSPERO REGISTRATION NO: CRD42021224975.

Glycemic Index Versus Wheat Fiber on Arterial Wall Damage in Diabetes: A Randomized Controlled Trial.

OBJECTIVE: High cereal fiber and low-glycemic index (GI) diets are associated with reduced cardiovascular disease (CVD) risk in cohort studies. Clinical trial evidence on event incidence is lacking. Therefore, to make trial outcomes more directly relevant to CVD, we compared the effect on carotid plaque development in diabetes of a low-GI diet versus a whole-grain wheat-fiber diet. RESEARCH DESIGN AND METHODS: The study randomized 169 men and women with well-controlled type 2 diabetes to counseling on a low GI-diet or whole-grain wheat-fiber diet for 3 years. Change in carotid vessel wall volume (VWV) (prespecified primary end point) was assessed by MRI as an indication of arterial damage. RESULTS: Of 169 randomized participants, 134 completed the study. No treatment differences were seen in VWV. However, on the whole-grain wheat-fiber diet, VWV increased significantly from baseline, 23 mm3 (95% CI 4, 41; P = 0.016), but not on the low-GI diet, 8 mm3 (95% CI -10, 26; P = 0.381). The low-GI diet resulted in preservation of renal function, as estimated glomerular filtration rate, compared with the reduction following the wheat-fiber diet. HbA1c was modestly reduced over the first 9 months in the intention-to-treat analysis and extended with greater compliance to 15 months in the per-protocol analysis. CONCLUSIONS: Since the low-GI diet was similar to the whole-grain wheat-fiber diet recommended for cardiovascular risk reduction, the low-GI diet may also be effective for CVD risk reduction.

Effect of Important Food Sources of Fructose-Containing Sugars on Inflammatory Biomarkers: A Systematic Review and Meta-Analysis of Controlled Feeding Trials.

BACKGROUND: Fructose-containing sugars as sugar-sweetened beverages (SSBs) may increase inflammatory biomarkers. Whether this effect is mediated by the food matrix at different levels of energy is unknown. To investigate the role of food source and energy, we conducted a systematic review and meta-analysis of controlled trials on the effect of different food sources of fructose-containing sugars on inflammatory markers at different levels of energy control. METHODS: MEDLINE, Embase, and the Cochrane Library were searched through March 2022 for controlled feeding trials ≥ 7 days. Four trial designs were prespecified by energy control: substitution (energy matched replacement of sugars); addition (excess energy from sugars added to diets); subtraction (energy from sugars subtracted from diets); and ad libitum (energy from sugars freely replaced). The primary outcome was C-reactive protein (CRP). Secondary outcomes were tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Independent reviewers extracted data and assessed risk of bias. GRADE assessed certainty of evidence. RESULTS: We identified 64 controlled trials (91 trial comparisons, n = 4094) assessing 12 food sources (SSB; sweetened dairy; sweetened dairy alternative [soy]; 100% fruit juice; fruit; dried fruit; mixed fruit forms; sweetened cereal grains and bars; sweets and desserts; added nutritive [caloric] sweetener; mixed sources [with SSBs]; and mixed sources [without SSBs]) at 4 levels of energy control over a median 6-weeks in predominantly healthy mixed weight or overweight/obese adults. Total fructose-containing sugars decreased CRP in addition trials and had no effect in substitution, subtraction or ad libitum trials. No effect was observed on other outcomes at any level of energy control. There was evidence of interaction/influence by food source: substitution trials (sweetened dairy alternative (soy) and 100% fruit juice decreased, and mixed sources (with SSBs) increased CRP); and addition trials (fruit decreased CRP and TNF-α; sweets and desserts (dark chocolate) decreased IL-6). The certainty of evidence was moderate-to-low for the majority of analyses. CONCLUSIONS: Food source appears to mediate the effect of fructose-containing sugars on inflammatory markers over the short-to-medium term. The evidence provides good indication that mixed sources that contain SSBs increase CRP, while most other food sources have no effect with some sources (fruit, 100% fruit juice, sweetened soy beverage or dark chocolate) showing decreases, which may be dependent on energy control. CLINICALTRIALS: gov: (NCT02716870).

Important Food Sources of Fructose-Containing Sugars and Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis of Controlled Trials.

Background: Fructose providing excess calories in the form of sugar sweetened beverages (SSBs) increases markers of non-alcoholic fatty liver disease (NAFLD). Whether this effect holds for other important food sources of fructose-containing sugars is unclear. To investigate the role of food source and energy, we conducted a systematic review and meta-analysis of controlled trials of the effect of fructose-containing sugars by food source at different levels of energy control on non-alcoholic fatty liver disease (NAFLD) markers. Methods and Findings: MEDLINE, Embase, and the Cochrane Library were searched through 7 January 2022 for controlled trials ≥7-days. Four trial designs were prespecified: substitution (energy-matched substitution of sugars for other macronutrients); addition (excess energy from sugars added to diets); subtraction (excess energy from sugars subtracted from diets); and ad libitum (energy from sugars freely replaced by other macronutrients). The primary outcome was intrahepatocellular lipid (IHCL). Secondary outcomes were alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Independent reviewers extracted data and assessed risk of bias. The certainty of evidence was assessed using GRADE. We included 51 trials (75 trial comparisons, n = 2059) of 10 food sources (sugar-sweetened beverages (SSBs); sweetened dairy alternative; 100% fruit juice; fruit; dried fruit; mixed fruit sources; sweets and desserts; added nutritive sweetener; honey; and mixed sources (with SSBs)) in predominantly healthy mixed weight or overweight/obese younger adults. Total fructose-containing sugars increased IHCL (standardized mean difference = 1.72 [95% CI, 1.08 to 2.36], p < 0.001) in addition trials and decreased AST in subtraction trials with no effect on any outcome in substitution or ad libitum trials. There was evidence of influence by food source with SSBs increasing IHCL and ALT in addition trials and mixed sources (with SSBs) decreasing AST in subtraction trials. The certainty of evidence was high for the effect on IHCL and moderate for the effect on ALT for SSBs in addition trials, low for the effect on AST for the removal of energy from mixed sources (with SSBs) in subtraction trials, and generally low to moderate for all other comparisons. Conclusions: Energy control and food source appear to mediate the effect of fructose-containing sugars on NAFLD markers. The evidence provides a good indication that the addition of excess energy from SSBs leads to large increases in liver fat and small important increases in ALT while there is less of an indication that the removal of energy from mixed sources (with SSBs) leads to moderate reductions in AST. Varying uncertainty remains for the lack of effect of other important food sources of fructose-containing sugars at different levels of energy control.

Association of Low- and No-Calorie Sweetened Beverages as a Replacement for Sugar-Sweetened Beverages With Body Weight and Cardiometabolic Risk: A Systematic Review and Meta-analysis.

Importance: There are concerns that low- and no-calorie sweetened beverages (LNCSBs) do not have established benefits, with major dietary guidelines recommending the use of water and not LNCSBs to replace sugar-sweetened beverages (SSBs). Whether LNCSB as a substitute can yield similar improvements in cardiometabolic risk factors vs water in their intended substitution for SSBs is unclear. Objective: To assess the association of LNCSBs (using 3 prespecified substitutions of LNCSBs for SSBs, water for SSBs, and LNCSBs for water) with body weight and cardiometabolic risk factors in adults with and without diabetes. Data Sources: Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched from inception through December 26, 2021. Study Selection: Randomized clinical trials (RCTs) with at least 2 weeks of interventions comparing LNCSBs, SSBs, and/or water were included. Data Extraction and Synthesis: Data were extracted and risk of bias was assessed by 2 independent reviewers. A network meta-analysis was performed with data expressed as mean difference (MD) or standardized mean difference (SMD) with 95% CIs. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) system was used to assess the certainty of the evidence. Main Outcomes and Measures: The primary outcome was body weight. Secondary outcomes were other measures of adiposity, glycemic control, blood lipids, blood pressure, measures of nonalcoholic fatty liver disease, and uric acid. Results: A total of 17 RCTs with 24 trial comparisons were included, involving 1733 adults (mean [SD] age, 33.1 [6.6] years; 1341 women [77.4%]) with overweight or obesity who were at risk for or had diabetes. Overall, LNCSBs were a substitute for SSBs in 12 RCTs (n = 601 participants), water was a substitute for SSBs in 3 RCTs (n = 429), and LNCSBs were a substitute for water in 9 RCTs (n = 974). Substitution of LNCSBs for SSBs was associated with reduced body weight (MD, -1.06 kg; 95% CI, -1.71 to -0.41 kg), body mass index (MD, -0.32; 95% CI, -0.58 to -0.07), percentage of body fat (MD, -0.60%; 95% CI, -1.03% to -0.18%), and intrahepatocellular lipid (SMD, -0.42; 95% CI, -0.70 to -0.14). Substituting water for SSBs was not associated with any outcome. There was also no association found between substituting LNCSBs for water with any outcome except glycated hemoglobin A1c (MD, 0.21%; 95% CI, 0.02% to 0.40%) and systolic blood pressure (MD, -2.63 mm Hg; 95% CI, -4.71 to -0.55 mm Hg). The certainty of the evidence was moderate (substitution of LNCSBs for SSBs) and low (substitutions of water for SSBs and LNCSBs for water) for body weight and was generally moderate for all other outcomes across all substitutions. Conclusions and Relevance: This systematic review and meta-analysis found that using LNCSBs as an intended substitute for SSBs was associated with small improvements in body weight and cardiometabolic risk factors without evidence of harm and had a similar direction of benefit as water substitution. The evidence supports the use of LNCSBs as an alternative replacement strategy for SSBs over the moderate term in adults with overweight or obesity who are at risk for or have diabetes.

Are fatty nuts a weighty concern? A systematic review and meta-analysis and dose-response meta-regression of prospective cohorts and randomized controlled trials.

Nuts are recommended for cardiovascular health, yet concerns remain that nuts may contribute to weight gain due to their high energy density. A systematic review and meta-analysis of prospective cohorts and randomized controlled trials (RCTs) was conducted to update the evidence, provide a dose-response analysis, and assess differences in nut type, comparator and more in subgroup analyses. MEDLINE, EMBASE, and Cochrane were searched, along with manual searches. Data from eligible studies were pooled using meta-analysis methods. Interstudy heterogeneity was assessed (Cochran Q statistic) and quantified (I2 statistic). Certainty of the evidence was assessed by Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Six prospective cohort studies (7 unique cohorts, n = 569,910) and 86 RCTs (114 comparisons, n = 5873) met eligibility criteria. Nuts were associated with lower incidence of overweight/obesity (RR 0.93 [95% CI 0.88 to 0.98] P < 0.001, "moderate" certainty of evidence) in prospective cohorts. RCTs presented no adverse effect of nuts on body weight (MD 0.09 kg, [95% CI -0.09 to 0.27 kg] P < 0.001, "high" certainty of evidence). Meta-regression showed that higher nut intake was associated with reductions in body weight and body fat. Current evidence demonstrates the concern that nut consumption contributes to increased adiposity appears unwarranted.

Different Food Sources of Fructose-Containing Sugars and Fasting Blood Uric Acid Levels: A Systematic Review and Meta-Analysis of Controlled Feeding Trials.

BACKGROUND: Although fructose as a source of excess calories increases uric acid, the effect of the food matrix is unclear. OBJECTIVES: To assess the effects of fructose-containing sugars by food source at different levels of energy control on uric acid, we conducted a systematic review and meta-analysis of controlled trials. METHODS: MEDLINE, Embase, and the Cochrane Library were searched (through 11 January 2021) for trials ≥ 7 days. We prespecified 4 trial designs by energy control: substitution (energy-matched replacement of sugars in diets); addition (excess energy from sugars added to diets); subtraction (energy from sugars subtracted from diets); and ad libitum (energy from sugars freely replaced in diets) designs. Independent reviewers (≥2) extracted data and assessed the risk of bias. Grading of Recommendations, Assessment, Development, and Evaluation was used to assess the certainty of evidence. RESULTS: We included 47 trials (85 comparisons; N = 2763) assessing 9 food sources [sugar-sweetened beverages (SSBs), sweetened dairy, fruit drinks, 100% fruit juice, fruit, dried fruit, sweets and desserts, added nutritive sweetener, and mixed sources] across 4 energy control levels in predominantly healthy, mixed-weight adults. Total fructose-containing sugars increased uric acid levels in substitution trials (mean difference, 0.16 mg/dL;  95% CI:  0.06-0.27 mg/dL;  P = 0.003), with no effect across the other energy control levels. There was evidence of an interaction by food source: SSBs and sweets and desserts increased uric acid levels in the substitution design, while SSBs increased and 100% fruit juice decreased uric acid levels in addition trials. The certainty of evidence was high for the increasing effect of SSBs in substitution and addition trials and the decreasing effect of 100% fruit juice in addition trials and was moderate to very low for all other comparisons. CONCLUSIONS: Food source more than energy control appears to mediate the effects of fructose-containing sugars on uric acid. The available evidence provides reliable indications that SSBs increase and 100% fruit juice decreases uric acid levels. More high-quality trials of different food sources are needed. This trial was registered at clinicaltrials.gov as NCT02716870.

The association of soluble CD163, a novel biomarker of macrophage activation, with type 2 diabetes mellitus and its underlying physiological disorders: A systematic review.

This systematic review investigates the association of sCD163, a novel biomarker of macrophage activation, with type 2 diabetes mellitus (T2DM), insulin resistance, and beta-cell dysfunction. Sixteen studies (seven cross-sectional, two case-control, one nested case-control, three prospective cohort, and three experimental) were identified. Most studies demonstrated that elevated sCD163 concentrations were associated with increased insulin resistance. Cross-sectional, case-control, and nested case-control studies showed higher sCD163 in subjects with T2DM compared with healthy individuals. An 18-year follow-up prospective cohort study showed that elevated baseline sCD163 was a strong predictor of T2DM incidence. Prospective cohort studies demonstrated that baseline measures and longitudinal changes in sCD163 were positively associated with insulin resistance; however, associations with beta-cell function were inconsistent. Two experimental studies evaluated the relationship of sCD163 with T2DM and HOMA-IR after weight-reducing interventions. After very low-calorie diet treatments, sCD163 concentration declined significantly in patients with T2DM but was not associated with insulin resistance. Bariatric surgery did not significantly impact sCD163 levels. In a double-blind randomized controlled trial, resveratrol supplementation significantly reduced circulating sCD163 in T2DM patients. Current studies demonstrate the potential utility of sCD163 as an early biomarker of T2DM risk and highlight a potential mechanism linking obesity with T2DM onset.

Supplemental Vitamins and Minerals for Cardiovascular Disease Prevention and Treatment: JACC Focus Seminar.

This is an update of the previous 2018 systematic review and meta-analysis of vitamin and mineral supplementation on cardiovascular disease outcomes and all-cause mortality. New randomized controlled trials and meta-analyses were identified by searching the Cochrane library, Medline, and Embase, and data were analyzed using random effects models and classified by the Grading of Recommendations Assessment Development and Evaluation approach. This updated review shows similar findings to the previous report for preventive benefits from both folic acid and B vitamins for stroke and has been graded with moderate quality. No effect was seen for the commonly used multivitamins, vitamin D, calcium, and vitamin C, and an increased risk was seen with niacin (with statin) for all-cause mortality. Conclusive evidence for the benefit of supplements across different dietary backgrounds, when the nutrient is sufficient, has not been demonstrated.

Effect of viscous fiber supplementation on obesity indicators in individuals consuming calorie-restricted diets: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Dietary fiber has played a consistent role in weight management, with efficacy potentially attributed to increased viscous fiber consumption. PURPOSE: To summarize the effects of viscous fiber on body weight and other anthropometric parameters, along with a calorie-deficient diet, through a systematic review and meta-analysis. METHODS: MEDLINE, EMBASE, and the Cochrane library were searched through July 24, 2019 for randomized controlled trials that assessed the effect of viscous fiber supplementation as part of a restricted calorie diet for ≥ 4 weeks relative to comparator diets. Data were pooled using the generic inverse-variance method with random-effects models and expressed as mean differences with 95% confidence intervals. Inter-study heterogeneity was assessed using Cochran's Q and quantified with I2. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the overall certainty of evidence. RESULTS: Findings from 15 studies (n = 1347) showed viscous fiber supplementation significantly decreased body weight (- 0.81 kg [- 1.20, - 0.41]; p < 0.0001), BMI (- 0.25 kg/m2 [- 0.46, - 0.05]; p = 0.01), and body fat (- 1.39% [- 2.61, - 0.17]; p = 0.03), compared to control. No effect on waist circumference was found. The certainty of evidence was graded as "moderate" for body weight, BMI, and body fat based on downgrades for imprecision. Waist circumference was graded "low" for downgrades of inconsistency and imprecision. CONCLUSION: Viscous fiber within a calorie-restricted diet significantly improved body weight and other markers of adiposity in overweight adults and those with additional risk factors for cardiovascular disease. This trial is registered at www.clinicaltrials.gov as NCT03257449. REGISTRATION: ClinicalTrials.gov identifier: NCT03257449.

Relation of Different Fruit and Vegetable Sources With Incident Cardiovascular Outcomes: A Systematic Review and Meta-Analysis of Prospective Cohort Studies.

Background Public health policies reflect concerns that certain fruit sources may not have the intended benefits and that vegetables should be preferred to fruit. We assessed the relation of fruit and vegetable sources with cardiovascular outcomes using a systematic review and meta-analysis of prospective cohort studies. Methods and Results MEDLINE, EMBASE, and Cochrane were searched through June 3, 2019. Two independent reviewers extracted data and assessed study quality (Newcastle-Ottawa Scale). Data were pooled (fixed effects), and heterogeneity (Cochrane-Q and I2) and certainty of the evidence (Grading of Recommendations Assessment, Development, and Evaluation) were assessed. Eighty-one cohorts involving 4 031 896 individuals and 125 112 cardiovascular events were included. Total fruit and vegetables, fruit, and vegetables were associated with decreased cardiovascular disease (risk ratio, 0.93 [95% CI, 0.89-0.96]; 0.91 [0.88-0.95]; and 0.94 [0.90-0.97], respectively), coronary heart disease (0.88 [0.83-0.92]; 0.88 [0.84-0.92]; and 0.92 [0.87-0.96], respectively), and stroke (0.82 [0.77-0.88], 0.82 [0.79-0.85]; and 0.88 [0.83-0.93], respectively) incidence. Total fruit and vegetables, fruit, and vegetables were associated with decreased cardiovascular disease (0.89 [0.85-0.93]; 0.88 [0.86-0.91]; and 0.87 [0.85-0.90], respectively), coronary heart disease (0.81 [0.72-0.92]; 0.86 [0.82-0.90]; and 0.86 [0.83-0.89], respectively), and stroke (0.73 [0.65-0.81]; 0.87 [0.84-0.91]; and 0.94 [0.90-0.99], respectively) mortality. There were greater benefits for citrus, 100% fruit juice, and pommes among fruit sources and allium, carrots, cruciferous, and green leafy among vegetable sources. No sources showed an adverse association. The certainty of the evidence was "very low" to "moderate," with the highest for total fruit and/or vegetables, pommes fruit, and green leafy vegetables. Conclusions Fruits and vegetables are associated with cardiovascular benefit, with some sources associated with greater benefit and none showing an adverse association. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT03394339.

Selenium, antioxidants, cardiovascular disease, and all-cause mortality: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Antioxidants have been promoted for cardiovascular disease (CVD) risk reduction and for the prevention of cancer. Our preliminary analysis suggested that only when selenium was present were antioxidant mixtures associated with reduced all-cause mortality. OBJECTIVE: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to determine the effect of selenium supplementation alone and of antioxidant mixtures with or without selenium on the risk of CVD, cancer, and mortality. METHODS: We identified studies using the Cochrane Library, Medline, and Embase for potential CVD outcomes, cancer, and all-cause mortality following selenium supplementation alone or after antioxidant supplement mixtures with and without selenium up to June 5, 2020. RCTs of ≥24 wk were included and data were analyzed using random-effects models and classified by the Grading of Recommendations, Assessment, Development, and Evaluation approach. RESULTS: The meta-analysis identified 9423 studies, of which 43 were used in the final analysis. Overall, no association of selenium alone or antioxidants was seen with CVD and all-cause mortality. However, a decreased risk with antioxidant mixtures was seen for CVD mortality when selenium was part of the mix (RR: 0.77; 95% CI: 0.62, 0.97; P = 0.02), with no association when selenium was absent. Similarly, when selenium was part of the antioxidant mixture, a decreased risk was seen for all-cause mortality (RR: 0.90; 95% CI: 0.82, 0.98; P = 0.02) as opposed to an increased risk when selenium was absent (RR: 1.09; 95% CI: 1.04, 1.13; P = 0.0002). CONCLUSION: The addition of selenium should be considered for supplements containing antioxidant mixtures if they are to be associated with CVD and all-cause mortality risk reduction. This trial was registered at https://www.crd.york.ac.uk/PROSPERO/ as CRD42019138268.

Association of Major Food Sources of Fructose-Containing Sugars With Incident Metabolic Syndrome: A Systematic Review and Meta-analysis.

Importance: Sugar-sweetened beverages (SSBs) are associated with increased risk of metabolic syndrome (MetS). However, the role of other important food sources of fructose-containing sugars in the development of MetS remains unclear. Objective: To examine the association of major food sources of fructose-containing sugars with incident MetS. Data Sources: MEDLINE, Embase, and Cochrane Library were searched from database inception to March 24, 2020, in addition to manual searches of reference lists from included studies using the following search terms: sugar-sweetened beverages, fruit drink, yogurt, metabolic syndrome, and prospective study. Study Selection: Inclusion criteria included prospective cohort studies of 1 year or longer that investigated the association of important food sources of fructose-containing sugars with incident MetS in participants free of MetS at the start of the study. Data Extraction and Synthesis: Study quality was assessed using the Newcastle-Ottawa Scale. Extreme quantile risk estimates for each food source with MetS incidence were pooled using a random-effects meta-analysis. Interstudy heterogeneity was assessed (Cochran Q statistic) and quantified (I2 statistic). Dose-response analyses were performed using a 1-stage linear mixed-effects model. The certainty of the evidence was assessed using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation). Results were reported according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. Main Outcomes and Measures: Pooled risk ratio (RR) of incident MetS (pairwise and dose response). Results: Thirteen prospective cohort studies (49 591 participants [median age, 51 years; range, 6-90 years]; 14 205 with MetS) that assessed 8 fructose-containing foods and MetS were included. An adverse linear dose-response association for SSBs (RR for 355 mL/d, 1.14; 95% CI, 1.05-1.23) and an L-shaped protective dose-response association for yogurt (RR for 85 g/d, 0.66; 95% CI, 0.58-0.76) and fruit (RR for 80 g/d, 0.82; 95% CI, 0.78-0.86) was found. Fruit juices (mixed and 100%) had a U-shaped dose-response association with protection at moderate doses (mixed fruit juice: RR for 125 mL/d, 0.58; 95% CI, 0.42-0.79; 100% fruit juice: RR for 125 mL/d, 0.77; 95% CI, 0.61-0.97). Honey, ice cream, and confectionary had no association with MetS incidence. The certainty of the evidence was moderate for SSBs, yogurt, fruit, mixed fruit juice, and 100% fruit juice and very low for all other food sources. Conclusions and Relevance: The findings of this meta-analysis suggest that the adverse association of SSBs with MetS does not extend to other food sources of fructose-containing sugars, with a protective association for yogurt and fruit throughout the dose range and for 100% fruit juice and mixed fruit juices at moderate doses. Therefore, current policies and guidelines on the need to limit sources of free sugars may need to be reexamined.

Can dietary viscous fiber affect body weight independently of an energy-restrictive diet? A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The role of dietary fiber in obesity management remains debatable. Evidence suggests that intake of viscous fiber may have the potential to facilitate weight loss. OBJECTIVE: We aimed to summarize and quantify the effects of viscous fiber on body weight, BMI, waist circumference, and body fat, independent of calorie restriction, through a systematic review and meta-analysis of randomized controlled trials. METHODS: Trials ≥4 wk in duration that assessed the effect of viscous fiber supplemented to an ad libitum diet along with comparator diets were included. MEDLINE, EMBASE, and the Cochrane library were searched through 24 July, 2019. Two independent reviewers extracted relevant data. Data were pooled using the generic inverse variance method and random-effects models and expressed as mean differences with 95% CIs. Interstudy heterogeneity was assessed (Cochran Q statistic) and quantified (I2 statistic). The overall certainty of evidence was explored using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. RESULTS: Findings from 62 trials (n = 3877) showed that viscous fiber reduced mean body weight (-0.33 kg; 95% CI: -0.51, -0.14 kg; P = 0.004), BMI (in kg/m2) (-0.28; 95% CI: -0.42, -0.14; P = 0.0001), and waist circumference (-0.63 cm; 95% CI: -1.11, -0.16 cm; P = 0.008), with no change in body fat (-0.78%; 95% CI: -1.56%, 0.00%; P = 0.05) when consumed with an ad libitum diet. Greater reductions in body weight were observed in overweight individuals and those with diabetes and metabolic syndrome. The certainty of evidence was graded moderate for body weight, high for waist circumference and body fat, and low for BMI. CONCLUSIONS: Dietary viscous fiber modestly yet significantly improved body weight and other parameters of adiposity independently of calorie restriction. Future trials are warranted to address the inconsistency and imprecision identified through GRADE and to determine long-term weight-loss sustainability.This systematic review and meta-analysis was registered at clinicaltrials.gov as NCT03257449.

Mediterranean diet, cardiovascular disease and mortality in diabetes: A systematic review and meta-analysis of prospective cohort studies and randomized clinical trials.

To update the clinical practice guidelines for nutrition therapy of the European Association for the Study of Diabetes, we conducted a systematic review and meta-analysis of prospective cohort studies and randomized clinical trials (RCTs) to evaluate the effect of the Mediterranean diet (MedDiet) on the prevention of cardiovascular disease (CVD) incidence and mortality. We searched Medline, EMBASE (through April 20, 2018) and Cochrane (through May 7, 2018) databases. Pooled relative risks (RRs) and 95% confidence interval (CI) were calculated by the generic inverse variance method. A total of 41 reports (3 RCTs and 38 cohorts) were included. Meta-analyses of RCTs revealed a beneficial effect of the MedDiet on total CVD incidence (RR: 0.62; 95% CI: 0.50, 0.78) and total myocardial infarction (MI) incidence (RR: 0.65; 95% CI: 0.49, 0.88). Meta-analyses of prospective cohort studies, which compared the highest versus lowest categories of MedDiet adherence, revealed an inverse association with total CVD mortality (RR: 0.79; 95% CI: 0.77, 0.82), coronary heart disease (CHD) incidence (RR: 0.73; 95% CI: 0.62, 0.86), CHD mortality (RR: 0.83; 95% CI: 0.75, 0.92), stroke incidence (RR: 0.80; 95% CI: 0.71, 0.90), stroke mortality (RR: 0.87; 95% CI: 0.80, 0.96) and MI incidence (RR: 0.73; 95% CI: 0.61, 0.88). The present study suggests that MedDiet has a beneficial role on CVD prevention in populations inclusive of individuals with diabetes.

Important Food Sources of Fructose-Containing Sugars and Incident Hypertension: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies.

Background Sugar-sweetened beverages are associated with hypertension. We assessed the relation of important food sources of fructose-containing sugars with incident hypertension using a systematic review and meta-analysis of prospective cohort studies. Methods and Results We searched MEDLINE, EMBASE, and Cochrane (through December week 2, 2018) for eligible studies. For each food source, natural log-transformed risk ratios (RRs) for incident hypertension were pooled using pair-wise meta-analysis and linear and nonlinear dose-response meta-analyses. Certainty in our evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation. We identified 26 reports, including 15 prospective cohorts (930 677 participants; 363 459 cases). Sugar-sweetened beverages showed harmful (RRper-355-mL, 1.10 [95% CI, 1.08, 1.12]) whereas fruit (RRper-240-g, 0.94 [95% CI, 0.96, 0.99]) and yogurt showed protective associations (RRper-125-g, 0.95 [95% CI, 0.94, 0.97]) with incident hypertension throughout the dose range. One hundred percent fruit juice showed a protective association only at moderate doses (RRat-100-mL, 0.97 [95% CI, 0.94, 0.99]). The pair-wise protective association of dairy desserts was not supported by linear dose-response analysis. Fruit drinks or sweet snacks were not associated with hypertension. Certainty of the evidence was "low" for sugar-sweetened beverages, 100% fruit juice, fruit, and yogurt and "very low" for fruit drinks, sweet snacks, and dairy desserts. Conclusions The harmful association between sugar-sweetened beverages and hypertension does not extend to other important food sources of fructose-containing sugars. Further research is needed to improve our estimates and better understand the dose-response relationship between food sources of fructose-containing sugars and hypertension. Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT02702375.