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

Abstract

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.

Keywords: LDL cholesterol; cardiovascular disease prevention; lipids; meta-analysis; soy protein; total cholesterol.

FIGURE 1

Study selection indicating the number of studies identified by the FDA and the number of studies included in the meta-analysis.

FIGURE 2

Forest plot for the effect of soy protein intake on circulating LDL cholesterol concentration in adults. Overall effect is represented by the black diamond. ¹Total n = 37, but reported n = 71 for soy protein diets and n = 72 for milk protein diets. ²Twelve subjects were excluded in data analysis in test 1 and 7 in test 2, but it was not specified from which arm; 50% dropout rate was taken from each. Data are expressed as mean differences with 95% CIs, using the generic inverse variance method with random effects models. Paired analyses were applied to all crossover studies. Interstudy heterogeneity was tested by the Cochran Q statistic at a significance level of P < 0.10 and quantified by I²; level of ≥50% represented substantial heterogeneity. n, number of participants.

FIGURE 3

Forest plot for the effect of soy protein intake on circulating TC concentration in adults. Overall effect is represented by the black diamond. ¹Total n = 37, but reported n = 71 for soy protein diets and n = 72 for milk protein diets. ²Twelve subjects were excluded in data analysis in test 1 and 7 in test 2, but it was not specified from which arm; 50% dropout rate was taken from each. Data are expressed as mean differences with 95% CIs, using the generic inverse variance method with random effects models. Paired analyses were applied to all crossover studies. Interstudy heterogeneity was tested by the Cochran Q statistic at a significance level of P < 0.10 and quantified by I²; level of ≥50% represented substantial heterogeneity. n, number of participants; TC, total cholesterol.