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A mutation in the gene for apolipoprotein B appears to be linked to elevated cholesterol levels, a condition called hypercholesterolemia. Researchers used gene analysis to identify a mutation called Arg3500Gln in a Danish population consisting of 9,255 from the general population, 948 with coronary heart disease and 36 with hereditary hypercholesterolemia. Blood cholesterol levels were significantly higher in those with this mutation and those with heart disease or hypercholesterolemia were much more likely to have the mutation. Apolipoprotein B is a protein that helps remove cholesterol from the blood.

Animal studies show beneficial effects of alcohol-extractable components of soy protein isolate on both atherogenic and antiatherogenic plasma lipoproteins. We tested the hypothesis that those components produce beneficial lipoprotein effects similarly in humans, in which case soy protein might be prepared to contain optimal amounts of alcohol-extractable components for use in preventive diets. Twelve healthy, normolipidemic subjects, six premenopausal women and six men, consumed three liquid-formula diets of identical composition except that they contained either unextracted or ethanol-extracted soy protein or casein. After 28-32 d, the unextracted soy protein diet did not lower total, LDL and VLDL cholesterol or apo B nor did it increase HDL cholesterol significantly compared with the extracted soy protein diet, although it did raise plasma apo AI 10% (P [is less than] 0.05). Furthermore, in women, VLDL cholesterol, total triglycerides and apo AII increased 40, 36 and 6% (P [is less than] 0.05), respectively. In men, however, the unextracted soy protein diet decreased the ratio of LDL to HDL cholesterol by 22% (P [is less than] 0.05). Most remarkably, unextracted soy protein increased the atherogenic lipoprotein(a) ~335% (P [is less than] 0.001) in both women and men. We conclude that alcohol-extractable components of soy protein increase several lipid risk factors and that in young women, in particular, the total lipid risk factor level appears to be increased. These data suggest that extracted rather than unextracted soy protein should be used in antiatherogenic diets.

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.].

We found previously that dietary soy protein, compared with casein, reduced plasma LDL cholesterol and increased HDL cholesterol concentrations in healthy women and men. However, there was considerable variation among individuals. The aim of this study was to characterize the lipoprotein responsiveness of individuals to examine whether different response patterns could be identified. Nine normolipemic men consumed 2 liquid-formula diets of identical composition except that the protein component was either soy protein or casein. After 1 mo of consuming each diet, the subjects’ plasma HDL cholesterol (P < 0.01) and apolipoprotein (apo) A-I (P < 0.05) concentrations were increased by the soy protein diet whereas the ratio of LDL cholesterol to HDL cholesterol was decreased (P < 0.01); total cholesterol, triacylglycerol, LDL cholesterol, apo B and apo A-II were insignificantly affected. In 5 individuals, however, soy protein reduced mean LDL cholesterol, LDL2 cholesterol, and LDL2 apo B concentrations by 26% and plasma apo B by 16%, whereas HDL cholesterol increased by 11% . In 3 other individuals, soy protein increased mean HDL cholesterol by 17% and plasma apo A-I by 12%, but did not lower LDL. In 1 subject, soy protein decreased LDL2 cholesterol by 11% and increased plasma triacylglycerol by 40%, but neither HDL cholesterol nor apo A-I increased. We identified 3 types of lipemic responses to dietary soy protein involving a reduction in atherogenic LDL and increase in antiatherogenic HDL. In most subjects, the effects on both LDL and HDL were favorable, although fewer experienced either an increase in HDL or a decrease in LDL2. [ABSTRACT FROM AUTHOR]

Background: Familial hypercholesterolemia leads to premature ischemic heart disease and is often caused by mutations in the gene for the low-density lipoprotein receptor. Mutations in the apolipoprotein B gene, which encodes a ligand for this receptor, may also result in this phenotype. Methods: We studied the genotypes of 9255 women and men from the general population, 948 patients with ischemic heart disease, and 36 patients with familial hypercholesterolemia, all from Denmark, for three mutations in the apolipoprotein B gene: Arg3500Gln, Arg3531Cys, and Arg3500Trp. Results: The prevalence of heterozygotes in the general population was 0.08 percent (95 percent confidence interval, 0.03 to 0.16 percent) for both the Arg3500Gln and the Arg3531Cys mutations, and 0.00 percent (95 percent confidence interval, 0.00 to 0.18 percent) for the Arg3500Trp mutation. Among carriers of the Arg3500Gln mutation, cholesterol levels were significantly higher than among noncarriers in the general population — by 100 mg per deciliter (2.6 mmol per liter) among carriers in the general population, 154 mg per deciliter (4.0 mmol per liter) among patients with ischemic heart disease, and 172 mg per deciliter (4.5 mmol per liter) among patients with familial hypercholesterolemia. Heterozygous carriers of the Arg3500Gln mutation were significantly more common among patients with ischemic heart disease (odds ratio, 7.0; 95 percent confidence interval, 2.2 to 22; P=0.003) and patients with familial hypercholesterolemia (odds ratio, 78; 95 percent confidence interval, 16 to 388; P=0.001) than in the general population. Heterozygous carriers of the Arg3531Cys mutation in the general population did not have higher-than-normal plasma cholesterol levels or an increased risk of ischemic heart disease (odds ratio; 1.4; 95 percent confidence interval, 0.2 to 11; P=0.54). Conclusions: The Arg3500Gln mutation in the apolipoprotein B gene, which is responsible for familial defective apolipoprotein B-100 and is present in approximately 1 in 1000 persons in Denmark, causes severe hypercholesterolemia and increases the risk of ischemic heart disease. (N Engl J Med 1998;338:1577-84.) [ABSTRACT FROM AUTHOR]