Cumulative Meta-Analysis of the Soy Effect Over Time.

Background Soy protein foods have attracted attention as useful plant protein foods with mild cholesterol-lowering effects that are suitable for inclusion in therapeutic diets. But on the basis of the lack of consistency in significant cholesterol reduction by soy in 46 randomized controlled trials, the US Food and Drug Administration (FDA) is reassessing whether the 1999 heart health claim for soy protein should be revoked. Methods and Results We have, therefore, performed a cumulative meta-analysis on the 46 soy trials identified by the FDA to determine if at any time, since the 1999 FDA final rule that established the soy heart health claim, the soy effect on serum cholesterol lost significance. The cumulative meta-analysis for both total cholesterol and low-density lipoprotein cholesterol demonstrated preservation of the small, but significant, reductions seen both before and during the subsequent 14 years since the health claim was originally approved. For low-density lipoprotein cholesterol, the mean reduction in 1999 was -6.3 mg/dL (95% CI, -8.7 to -3.9 mg/dL; P=0.00001) and remained in the range of -4.2 to -6.7 mg/dL ( P=0.0006 to P=0.0002, respectively) in the years after 1999. At no time point did the total cholesterol or low-density lipoprotein cholesterol reductions lose significance or were the differences at individual time points in the cumulative meta-analysis significantly different from those seen in 1999 when the health claim was approved. Conclusions A cumulative meta-analysis of the data selected by the FDA indicates continued significance of total cholesterol and low-density lipoprotein cholesterol reduction after soy consumption and supports the rationale behind the original soy FDA heart health claim.

A Meta-Analysis of 46 Studies Identified by the FDA Demonstrates that Soy Protein Decreases Circulating LDL and Total Cholesterol Concentrations in Adults.

BACKGROUND: Certain plant foods (nuts and soy protein) and food components (viscous fibers and plant sterols) have been permitted by the FDA to carry a heart health claim based on their cholesterol-lowering ability. The FDA is currently considering revoking the heart health claim for soy protein due to a perceived lack of consistent LDL cholesterol reduction in randomized controlled trials. OBJECTIVE: We performed a meta-analysis of the 46 controlled trials on which the FDA will base its decision to revoke the heart health claim for soy protein. METHODS: We included the 46 trials on adult men and women, with baseline circulating LDL cholesterol concentrations ranging from 110 to 201 mg/dL, as identified by the FDA, that studied the effects of soy protein on LDL cholesterol and total cholesterol (TC) compared with non-soy protein. Two independent reviewers extracted relevant data. Data were pooled by the generic inverse variance method with a random effects model and expressed as mean differences with 95% CI. Heterogeneity was assessed and quantified. RESULTS: Of the 46 trials identified by the FDA, 43 provided data for meta-analyses. Of these, 41 provided data for LDL cholesterol, and all 43 provided data for TC. Soy protein at a median dose of 25 g/d during a median follow-up of 6 wk decreased LDL cholesterol by 4.76 mg/dL (95% CI: -6.71, -2.80 mg/dL, P < 0.0001; I2 = 55%, P < 0.0001) and decreased TC by 6.41 mg/dL (95% CI: -9.30, -3.52 mg/dL, P < 0.0001; I2 = 74%, P < 0.0001) compared with non-soy protein controls. There was no dose-response effect or evidence of publication bias for either outcome. Inspection of the individual trial estimates indicated most trials (∼75%) showed a reduction in LDL cholesterol (range: -0.77 to -58.60 mg/dL), although only a minority of these were individually statistically significant. CONCLUSIONS: Soy protein significantly reduced LDL cholesterol by approximately 3-4% in adults. Our data support the advice given to the general public internationally to increase plant protein intake. This trial was registered at clinicaltrials.gov as NCT03468127.

Effect of Plant Protein on Blood Lipids: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: There is a heightened interest in plant-based diets for cardiovascular disease prevention. Although plant protein is thought to mediate such prevention through modifying blood lipids, the effect of plant protein in specific substitution for animal protein on blood lipids remains unclear. To assess the effect of this substitution on established lipid targets for cardiovascular risk reduction, we conducted a systematic review and meta-analysis of randomized controlled trials using the Grading of Recommendations Assessment, Development, and Evaluation system. METHODS AND RESULTS: MEDLINE, EMBASE, and the Cochrane Registry were searched through September 9, 2017. We included randomized controlled trials of ≥3 weeks comparing the effect of plant protein in substitution for animal protein on low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B. Two independent reviewers extracted relevant data and assessed risk of bias. Data were pooled by the generic inverse variance method and expressed as mean differences with 95% confidence intervals. Heterogeneity was assessed (Cochran Q statistic) and quantified (I2 statistic). The overall quality (certainty) of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation system. One-hundred twelve randomized controlled trials met the eligibility criteria. Plant protein in substitution for animal protein decreased low-density lipoprotein cholesterol by 0.16 mmol/L (95% confidence interval, -0.20 to -0.12 mmol/L; P<0.00001; I2=55%; moderate-quality evidence), non-high-density lipoprotein cholesterol by 0.18 mmol/L (95% confidence interval, -0.22 to -0.14 mmol/L; P<0.00001; I2=52%; moderate-quality evidence), and apolipoprotein B by 0.05 g/L (95% confidence interval, -0.06 to -0.03 g/L; P<0.00001; I2=30%; moderate-quality evidence). CONCLUSIONS: Substitution of plant protein for animal protein decreases the established lipid targets low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B. More high-quality randomized trials are needed to improve our estimates. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02037321.

Dietary pulses, satiety and food intake: a systematic review and meta-analysis of acute feeding trials.

OBJECTIVE: To assess the effect of dietary pulses (beans, peas, chickpeas, lentils) on acute satiety and second meal intake, a systematic review and meta-analysis was conducted. METHODS: MEDLINE, EMBASE, CINAHL, and the Cochrane Registry (through May 6, 2013) were searched for acute controlled trials examining the effect of dietary pulses on postprandial satiety or second meal intake compared with isocaloric controls. Two independent reviewers extracted data and assessed methodological quality and risk of bias. Data were pooled by generic inverse variance random effects models and expressed as ratio of means (RoMs) for satiety and mean differences (MDs) for second meal food intake, with 95% confidence intervals (95% CIs). Heterogeneity was assessed (Q statistic) and quantified (I(2) statistic). Protocol registration: clinicaltrials.gov identifier, NCT01605422. RESULTS: Nine trials met the eligibility criteria. Dietary pulses produced a 31% greater satiety incremental area under the curve (IAUC) (RoM = 1.31, 95% CI: 1.09 to 1.58, P = 0.004; Phet = 0.96; I(2) = 0%) without affecting second meal intake (MD = -19.94, 95% CI: -75-35, P = 0.48; Phet = 0.01; I(2) = 63%). Our data are limited by the small sample sizes, narrow participant characteristics and significant unexplained heterogeneity among the available trials. CONCLUSIONS: Pooled analyses show that dietary pulses contribute to acute satiety but not second meal intake.