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

Arch Intern Med. 1999 Sep 27;159(17):2070-6. doi: 10.1001/archinte.159.17.2070.


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 (>4.24 mmol/L [>164 mg/dL]), comparable reductions were 9% (P<.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 Program Step I diet. Ethanol-extracted isolated soy protein did not significantly reduce plasma concentrations of total or LDL cholesterol.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Caseins / chemistry
  • Caseins / pharmacology*
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Double-Blind Method
  • Female
  • Humans
  • Isoflavones / analysis
  • Isoflavones / pharmacology*
  • Lipids / blood*
  • Lipoprotein(a) / blood
  • Male
  • Middle Aged
  • Soybean Proteins / chemistry
  • Soybean Proteins / pharmacology*
  • Triglycerides / blood


  • Caseins
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Isoflavones
  • Lipids
  • Lipoprotein(a)
  • Soybean Proteins
  • Triglycerides