Characteristics of the Studies

Table 1. Table 1. Characteristics of the 38 Studies.

Table 1 shows selected characteristics of the studies that met the criteria for analysis. The 29 articles chosen included the findings of 38 clinical studies; some articles reported data for different subgroups of subjects from one study (e.g., those with normal and those with high cholesterol concentrations); others reported on two different clinical studies. The 38 clinical studies were analyzed independently. in 4 studies the subjects were children, whereas in 34 they were adults. Most studies included both men and women, but the data necessary to analyze effects of soy protein according to sex were not available. Most studies used random assignment with crossover design. Twenty studies used isolated soy protein, 15 used textured soy protein, and 3 used a combination of the two. Soy protein intake averaged 47 g per day (range, 17 to 124); in 14 studies (37 percent) intake was <31 g per day.

In most studies the investigators attempted to provide similar amounts of total fat and saturated fat in the control and soy-containing diets. In 14 studies the diets were similar to conventional Western diets in fat and cholesterol content (these were termed “usual” diets), and in 18 studies the diets were low in fat content (<30 percent of energy) and low in cholesterol content (<200 mg per day). In 29 studies the amounts of total fat and saturated fat were similar in the control and soy-containing diets (i.e., they differed by less than 10 percent); 8 other studies were designed to provide similar total fat and saturated fat intake but the similarity of the diets was not documented. In 20 studies cholesterol intake was similar in the two diets; 9 other studies were designed to provide similar cholesterol intake but similarity was not documented.

All the studies except one37 were designed to maintain weight; 34 studies reported similar weight changes for subjects ingesting the control and soy-containing diets. In all, 19 studies had control and soy-containing diets that were similar with respect to intake of dietary fat (total and saturated), intake of dietary cholesterol, and weight change. These 19 studies are listed as “similar” in each of the last three columns of Table 1.

Changes in Serum Lipid Concentrations

Table 2. Table 2. Net Change in Serum Lipids and Lipoprotein Concentrations in Subjects Ingesting the Soy-Containing Diets, as Compared with the Control Diets.

The ingestion of diets containing soy protein, as compared with the control diets, was accompanied by a significant reduction in serum concentrations of total cholesterol, LDL cholesterol, and triglycerides (Table 2). The net change (change during the soy diet minus change during the control diet) in serum cholesterol concentrations was a decrease of 23.2 mg per deciliter (0.60 mmol per liter; 95 percent confidence interval for the decrease, 13.5 to 32.9 mg per deciliter [0.35 to 0.85 mmol per liter]), or 9.3 percent. Of 38 studies, 34 (89 percent) reported a net decrease and 4 (11 percent) reported a net increase in serum cholesterol concentrations.

Figure 1. Figure 1. Net Changes in Serum LDL Cholesterol Concentrations in 31 Clinical Trials of the Effects of Soy Protein on Serum Lipids. These 31 trials presented data on LDL cholesterol for a total of 564 subjects. The values shown are the mean changes in LDL cholesterol concentrations while subjects received the diet containing soy protein minus the changes during the control diet, with 95 percent confidence intervals. A and B indicate separate studies reported in a single published article, listed here in the same order as in Table 1. To convert values to millimoles per liter, multiply by 0.02586.

The net change in serum LDL cholesterol concentrations was a decrease of 21.7 mg per deciliter (0.56 mmol per liter; 95 percent confidence interval for the decrease, 11.2 to 31.7 mg per deciliter [0.30 to 0.82 mmol per liter]), or 12.9 percent. Figure 1 illustrates the net effects of the consumption of soy protein on serum LDL cholesterol concentrations as reported in 31 studies. Twenty-six studies (84 percent) reported a net reduction, four studies (13 percent) reported an increase, and one study (3 percent) reported no change.

Soy protein intake did not significantly affect serum HDL cholesterol concentrations, but the net change was an increase of 2.4 percent. Serum very-low-density lipoprotein (VLDL) cholesterol concentrations were not significantly altered by soy protein. The consumption of soy protein significantly decreased serum triglyceride concentrations, by 13.3 mg per deciliter (0.15 mmol per liter; 95 percent confidence interval for the decrease, 0.3 to 25.7 mg per deciliter [0.003 to 0.29 mmol per liter]), or 10.5 percent. Of 30 studies, 22 (73 percent) reported a net decrease in serum triglyceride concentrations, whereas 8 (27 percent) reported an increase.

Effect of Initial Serum Lipid Concentrations

Table 3. Table 3. Fixed-Effects Estimates from the Regression Model Predicting Net Changes in Serum Cholesterol Concentrations as a Function of Characteristics of the Study.

Table 3 summarizes the effects of various factors on changes in serum cholesterol concentrations. In the complete regression model, the initial serum cholesterol concentration was the only significant predictor of the change in the serum cholesterol concentration (P<0.001). The relation between the initial serum cholesterol concentration and changes in serum cholesterol was modeled as a quadratic polynomial function. The proportion reduction in variance among studies between conditional and unconditional models indicated that the base-line cholesterol concentration accounted for approximately 77 percent of the overall variance. However, significant heterogeneity continued to be present in the model even after adjustment for hypothesized predictors of variation (variance component = 0.134, P<0.001).

Table 4. Table 4. Changes in Serum Cholesterol and LDL Cholesterol Concentrations According to Quartiles of the Study Group for Initial Cholesterol Concentration.

Table 4 presents changes in serum cholesterol and LDL cholesterol concentrations according to quartiles of the initial cholesterol concentration. Subjects with normal cholesterol levels, who had initial values below 200 mg per deciliter, had nonsignificant reductions of 3.3 percent while receiving the soy protein diet. Those with mild hypercholesterolemia, who had initial values of 200 to 255 mg per deciliter (5.2 to 6.6 mmol per liter), had nonsignificant reductions of 4.4 percent. Subjects with moderate hypercholesterolemia, who had initial values of 259 to 333 mg per deciliter (6.70 to 8.61 mmol per liter), had significant decreases of 7.4 percent. Subjects with severe hypercholesterolemia, whose initial values were above 335 mg per deciliter (8.66 mmol per liter), had significant reductions of 19.6 percent.

The pattern of changes in serum LDL cholesterol concentrations, according to quartiles of the initial serum cholesterol values, was similar to the pattern for serum cholesterol concentrations: first quartile, a decrease of 7.7 percent; second quartile, a decrease of 6.8 percent; third quartile, a decrease of 9.8 percent; and fourth quartile, a decrease of 24.0 percent. Changes in serum HDL cholesterol concentrations were similar for all quartiles. Changes in serum triglyceride concentrations were significantly related to the initial serum triglyceride concentrations (P<0.05). However, changes in individual quartile groups were not statistically significant.

Effect of Other Variables

As shown in Table 3, the type of soy protein did not have a significant effect on the net change in serum cholesterol concentrations and accounted for only approximately 1.0 percent of the variance. The amount of soy protein in the diet was also not significant (P = 0.39) when net changes were assessed. The type of diet, although not statistically significant, accounted for approximately 12.6 percent of the variance (P = 0.07); larger changes tended to occur when the control diets were “usual” diets rather than low-fat and low-cholesterol diets. The results of studies of adult subjects did not differ significantly from those of the four studies of children; the age group of the subjects thus had a negligible effect on variance. The changes in the 19 studies with similar diets in terms of fat and cholesterol intake and weight change did not differ significantly from the changes in the remaining studies, in which the diets were not similar; this factor accounted for negligible variance.

To examine the effects of the type and amount of soy protein further, we performed a complete regression analysis using changes observed with the soy diet alone instead of net changes (soy diet minus control diet) as the outcome variable. In this model, significant effects were obtained for the initial serum cholesterol concentration (P<0.001; proportion of reduction accounted for, 0.69) and the amount of soy protein (P = 0.02; proportion of reduction, 0.13). This model predicted that soy protein intake would be associated with the following decreases in serum cholesterol concentrations, after adjustment for the initial values and other variables: 25 g per day of soy protein, a decrease of 8.9 mg per deciliter (0.23 mmol per liter); 50 g per day of soy protein, a decrease of 17.4 mg per deciliter (0.45 mmol per liter); and 75 g per day of soy protein, a decrease of 26.3 mg per deciliter (0.68 mmol per liter). The type of soy protein (P = 0.16), the type of diet (P = 0.11), the age group of the subjects (adults or children) (P = 0.39), and the similarity of the diets (P = 0.28) did not have significant effects on this model.