A Randomized Trial Comparing the Effect of Casein With That of Soy Protein Containing Varying Amounts of Isoflavones on Plasma Concentrations of Lipids and Lipoproteins

Abstract

Context: Isolated soy protein reduces plasma concentrations of total and low-density lipoprotein (LDL) cholesterol.Objective: To identify the agent(s) responsible for the cholesterol-lowering effect of soy in mildly hypercholesterolemic volunteers: isoflavones isolated together with soy protein or soy protein itself.Design: Double-blind randomized parallel trial.Setting: Single-center study.Participants: A total of 156 healthy men and women with LDL cholesterol levels between 3.62 mmol/L (140 mg/dL) and 5.17 mmol/L (200 mg/dL) after instruction in a National Cholesterol Education Program Step I diet and recruited by advertisement from the community.Intervention: One of 5 daily diets (25 g of casein [for isoflavone-free comparison] or 25 g of isolated soy protein containing 3, 27, 37, or 62 mg of isoflavones). Main Outcome Measures:Change and percent change from baseline in plasma concentrations of triglycerides and total, LDL, and high-density lipoprotein cholesterol after 9 weeks.Results: Compared with casein, isolated soy protein with 62 mg of isoflavones lowered total and LDL cholesterol levels by 4% (P = .04) and 6% (P = .01), respectively. In patients with LDL cholesterol levels in the top half of the population studied (Ͼ4.24 mmol/L [Ͼ164 mg/dL]), comparable reductions were 9% (PϽ.001) and 10% (P = 001), respectively; in this group, isolated soy protein with 37 mg of isoflavones reduced total (P = .007) and LDL (P = .02) cholesterol levels by 8%, and there was a dose-response effect of increasing amounts of isoflavones on total and LDL cholesterol levels. Plasma concentrations of triglycerides and high-density lipoprotein cholesterol were unaffected. Ethanol-extracted isolated soy protein containing 3 mg of isoflavones did not significantly reduce plasma concentrations of total or LDL cholesterol.Conclusions: Naturally occurring isoflavones isolated with soy protein reduce the plasma concentrations of total and LDL cholesterol without affecting concentrations of triglycerides or high-density lipoprotein cholesterol in mildly hypercholesterolemic volunteers consuming a National Cholesterol Education ProgramStep I diet. Ethanol-extracted isolated soy protein did not significantly reduce plasma concentrations of total or LDL cholesterol.

A biochanin-enriched isoflavone from red clover lowers LDL cholesterol in men

“…Many of the trials included in the large metaanalysis of soy protein failed to lower LDL-C. Other recent trials have also not found differences between soy protein isolates and control proteins, mostly casein (Gardner et al, 2001;Teede et al, 2001). By contrast, Crouse et al (1999) showed a clear soy isoflavone-related effect on LDL-C. Despite the large number of subjects in that study, 156 women and men, there was no clear genderisoflavone interaction, since LDL-C lowering was of marginal significance in the postmenopausal women (P ¼ 0.07) and in the men; premenopausal women showed no change.…”

“…The isoflavone content is likely to contribute strongly, since isoflavone-depleted soy protein appears less effective (Gardner et al, 2001;Wangen et al, 2001) and one large study has shown a dose-related effect when increasing amounts of isoflavones within soy protein were compared (Crouse et al, 1999). However, trials of purified isoflavones have to date been disappointing (Nestel et al, 1997(Nestel et al, , 1999Hodgson et al, 1998;Howes et al, 2000;Simons et al, 2000).…”

“…Among recent well-designed and executed trials, the reduction in non-high-density lipoprotein cholesterol (HDL-C) has been as low as 2.6% (Teixeira et al, 2000) or that of LDL-C no greater than with the milk protein-based control diets (Teede et al, 2001;Meinertz et al, 2002). As is seen with other cholesterol-lowering nutritional interventions, the best responses to soy protein were shown by individuals with the highest initial LDL-C levels (Crouse et al, 1999;Vigna et al, 2000). On the other hand, two recent studies that compared two soy protein products with very different isoflavone contents reported no specific LDL-C lowering attributable to isoflavones (Jenkins et al, 2002;Lichtenstein et al, 2002).…”

“…On the other hand, two recent studies that compared two soy protein products with very different isoflavone contents reported no specific LDL-C lowering attributable to isoflavones (Jenkins et al, 2002;Lichtenstein et al, 2002). Studies with intact soy protein have been conducted in both men and women with no apparent gender difference (Crouse et al, 1999). Adding to these variables is the large interindividual variation in isoflavone absorption (Tsunoda et al, 2002).…”

Neurobehavioral effects of dietary soy phytoestrogens

“…At the time, there was no recognition of a protective effect from isoflavones due to a paucity of data, but subsequent studies have shown that the cholesterollowering effect is influenced in a dose-dependent manner by the presence of isoflavones in the protein matrix [25,117]. Furthermore, data collected thus far in animals and from limited clinical trials show that isoflavones have protective or no effects on bone [8,29,62,93,100].…”