Lydeking-Olsen, Eva, Meinertz, Hans, Nilausen, Karin, Setchell, Kenneth D.R., Damhus, Mia, and Jensen, Trine Holm
BACKGROUND. Although the protein component of soybeans has been extensively studied for its effects on plasma lipids when taken as a dietary complement, soymilk--a more complete soybean product--has received limited attention and little is known about its long-term effects. Likewise, transdermal progesterone has not previously been evaluated for its lipoprotein effects. AIM: To evaluate the effect on plasma lipoproteins and tolerance of 2 y of soymilk consumption (400-500 mL/d) supplying 14-17.5 g/d of dietary protein and of use of transdermal progesterone, 25 mg/d. Two soymilk preparations were used: one with intact soy protein and a high isoflavone content (100 mg isoflavones per day) prepared from whole soybeans, and one prepared from alcohol-extracted soy protein free of isoflavones. Two transdermal preparations were tested, one with and one without progesterone. DESIGN: Normo- and hypercholesterolemic (plasma cholesterol, mean 254 mg/dL, range 170-387 mg/dL [6.58, 4.40-10.02 mmol/ L]), postmenopausal (age, mean 58 y, range 41-75 y) Caucasian women were randomly assigned to one of four treatment arms: isoflavone-rich soymilk and transdermal progesterone placebo (n = 22), isoflavone-free soymilk plus transdermal progesterone (n = 21), transdermal progesterone plus isoflavone-free soymilk (n = 21), isoflavone-rich soymilk plus transdermal progesterone (n = 21), and isoflavone-free soymilk and transdermal progesterone placebo (n = 20). Fasting plasma total cholesterol, triglycerides, and HDL cholesterol (HDL-C) (after precipitation of apo-[BETA]--containing lipoproteins) were measured by enzymatic procedures on fresh samples at baseline and after 6, 12, and 24 mo; LDL cholesterol (LDL-C) was calculated by the Friedewald formula. RESULTS: Eighty-four of 107 women completed the 2-y study. The randomization was successful to the extent that baseline plasma total cholesterol, LDL-C, and ratio of total cholesterol to HDL-C were insignificantly different between treatment groups; plasma triglycerides and HDL-C, however, showed significant variation between groups. A comparison of baseline and 2-y values showed that whereas isoflavone-free soymilk increased HDL-C significantly (8%, P < 0.05), isoflavone-rich soymilk both increased HDL-C (+7%, P < 0.05) and lowered LDL-C (-10%, P < 0.05) and the total cholesterol-HDL-C ratio (-11%, P < 0.001). Transdermal progesterone together with isoflavone-free soymilk decreased LDL-C (-14%, P < 0.019) and the total cholesterol--HDL-C ratio (-11%, P < 0.05), and transdermal progesterone together with isoflavone-rich soymilk likewise decreased LDL-C (-10%, P < 0.01) and the total cholesterol--HDL-C ratio (-8%, P < 0.05). CONCLUSION: Soymilk, in the absence of progesterone, increased HDL-C. When the protein was intact and the isoflavone content high, it also reduced LDL-C and the ratio of total cholesterol to HDL-C. Progesterone together with either of the two soymilk preparations decreased LDL-C and the ratio of total cholesterol to HDL-C. It was without effect on HDL-C. Thus, the two bone-protective treatments--soymilk with intact protein and high isoflavone content and soymilk with alcohol-extracted protein plus progesterone--both reduced atherogenic LDL-C and lowered the ratio of total cholesterol to HDL-C. In addition, the former of the treatments increased HDL-C. This is the first long-term study of soymilk consumption demonstrating beneficial effects on atherogenic and protective plasma lipoproteins with a relatively low intake of soymilk supplying 14-17 g/d of protein. It is also the first long-term study of transdermal progesterone demonstrating favorable effects on atherogenic lipoproteins. [Acknowledgments: Soy milk and placebo provided by ALPRO, Belgium, Proderma[R] and placebo by Phillips Nutritionals, Nevada, USA and Osforte[R] by Genese A/S, Denmark. Study supported by grants from the Danish Ministry of Health, Fondation Idella, Glunz and Jensen Foundation, Civilingenieur Frode V. Nyegaard and Wife's Foundation, Director E. Danielsen and Wife Foundation and IMK Foundation.].