Zhuo XG, Melby MK, Watanabe S. Soy isoflavone intake lowers serum LDL cholesterol: a meta-analysis of 8 randomized controlled trials in humans. J Nutr 134, 2395-2400

Department of Nutrition Science, Faculty of Applied Bioscience, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya, Tokyo 156-8502, Japan.
Journal of Nutrition (Impact Factor: 3.88). 09/2004; 134(9):2395-400.
Source: PubMed


Clinical trials have noted hypocholesterolemic effects of soy protein intake, but the components responsible are not known. This meta-analysis of 8 randomized controlled trials was conducted to more precisely evaluate the effects of isoflavones on blood LDL cholesterol concentration independently of soy protein level. PubMed was searched for English-language "randomized controlled trial" articles published from 1966 to 2003 that described the effects of soy protein isolate (SPI) intake with measured isoflavone levels on blood lipids in humans using the search terms "soy protein," "isoflavones," and "cholesterol." From 31 articles identified by the search, 8 articles (with 10 low vs. high isoflavone comparisons) were selected for the meta-analysis. Subjects in each comparison consumed similar dietary fat, cholesterol, and fiber; the reported body weight of subjects did not change significantly during treatment. Serum LDL cholesterol concentration in subjects who consumed SPI (mean 50 g/d) with high isoflavone content (mean intake 96 mg/d) decreased by 0.15 mmol/L (95% CI: 0.08 to 0.23 mmol/L; P < 0.0001) compared with those who consumed the same SPI level with low isoflavone content (mean intake 6 mg/d). Decreases in serum LDL cholesterol concentration in hypercholesterolemic and normocholesterolemic subjects were 0.18 mmol/L (95% CI: 0.01 to 0.35 mmol/L; P = 0.03) and 0.14 mmol/L (95% CI: 0.06, 0.23 mmol/L; P = 0.0008), respectively. With identical soy protein intake, high isoflavone intake led to significantly greater decreases in serum LDL cholesterol than low isoflavone intake, demonstrating that isoflavones have LDL cholesterol-lowering effects independent of soy protein.

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    • "But their hypolipidemic effects are inconsistent in human studies. When provided concurrently with soy protein, soy isoflavones exert synergistic or additive cholesterol-lowering effects (Zhuo et al., 2004; Zhan and Ho, 2005). In a meta-analysis of 11 randomized controlled trials, soy isoflavones significantly reduced serum TC and LDL-C but did not change HDL-C and TG, while reductions in LDL-C were larger in hypercholesterolemic than in normocholesterolemic subjects (Taku et al., 2007). "
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    ABSTRACT: Hyperlipidemia is one of the major risk factor for the development of cardiovascular disease. Hypolipidemic nutraceuticals and functional foods help improve serum lipid profiles as reducing total cholesterol, triglyceride, and low-density lipoprotein cholesterol, while elevating high-density lipoprotein cholesterol. The effectiveness of omega-3 polyunsaturated fatty acid, phytosterols, dietary fiber, and tea catechin in management of hyperlipidemia has been clearly demonstrated in epidemiological and interventional trials. Studies on mechanism reveal that they act as inhibitor or activator of critical enzyme, agonist or inhibitor of transcription factor, competitor of transporter, and sequestrant of bile acid to modulate lipid homeostasis. Hypolipidemic effects are also claimed in dietary proteins, many polyphenols, other phytochemicals, raw extract, or even whole food. This review attempts to give an overview of lipid homeostasis and summarize recent findings of hypolipidemic nutraceuticals and functional foods according to their active ingredients, focusing on the efficacy and underlying mechanisms.
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    • "However, recently the focus has been directed towards their effects on lipid metabolism. Data obtained from animal experiments as well as clinical and epidemiological studies suggest that consumption of isoflavones may prevent obesity [3] [4], type 2 diabetes [4], atherosclerosis [5], nonalcoholic fatty liver disease [6], and dyslipidaemia [7] [8]. Thus isoflavones might be useful in targeting the metabolic syndrome. "
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    ABSTRACT: Consumption of isoflavones may prevent adiposity, hepatic steatosis, and dyslipidaemia. However, studies in the area are few and primarily with genistein. This study investigated the effects of formononetin and its synthetic analogue, 2-heptyl-formononetin (C7F), on lipid and cholesterol metabolism in C57BL/6J mice. The mice were fed a cholesterol-enriched diet for five weeks to induce hypercholesterolemia and were then fed either the cholesterol-enriched diet or the cholesterol-enriched diet-supplemented formononetin or C7F for three weeks. Body weight and composition, glucose homeostasis, and plasma lipids were compared. In another experiment, mice were fed the above diets for five weeks, and hepatic triglyceride accumulation and gene expression and histology of adipose tissue and liver were examined. Supplementation with C7F increased plasma HDL-cholesterol thereby increasing the plasma level of total cholesterol. Supplementation with formononetin did not affect plasma cholesterol but increased plasma triglycerides levels. Supplementation with formononetin and C7F induced hepatic steatosis. However, formononetin decreased markers of inflammation and liver injury. The development of hepatic steatosis was associated with deregulated expression of hepatic genes involved in lipid and lipoprotein metabolism. In conclusion, supplementation with formononetin and C7F to a cholesterol-enriched diet adversely affected lipid and lipoprotein metabolism in C57BL/6J mice.
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    • "This could promote a greater NO bioavailability, contributing to the vasodilatation that has been previously described when genistein was given in the diet (Smith et al. 2005). Beyond its antioxidant properties, isoflavone actions include hypocholesterolemic (Zhuo et al. 2004), blood-pressure-lowering (Welty et al. 2007) and estrogen-like effects (Lissin and Cooke 2000), which contribute to reduce cardiovascular risk factors. These combined effects may be relevant in the reduction of cardiovascular events. "
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    ABSTRACT: This study analyzed and compared the content of isoflavones in 2 soy products, the effectiveness of isoflavones as antioxidants, in vitro, and demonstrated the antioxidant effect of a soy diet in rats with myocardial infarction (MI). Isoflavone content was analyzed in soybean hypocotyl (SH) and isolated soy protein (ISP). The quality (TAR) and quantity (TRAP) of antioxidants present in the samples was quantified. The amount of daidzin was higher in SH (9 times) and genistein in ISP (5 times). SH presented a 3-fold increase in TAR, while both products exhibited same TRAP. The rats were fed an ISP diet for 9 weeks. Animals were distributed among 6 treatment groups: (i) Sham Casein; (ii) Infarct Casein < 25%; (iii) Infarct Casein > 25%; (iv) Sham Soy; (v) Infarct Soy < 25%; and (vi) Infarct Soy > 25%. MI was induced 5 weeks after the commencement of the diets. Lipid peroxidation (LPO), antioxidant enzyme activity, and levels of nitrites/nitrates were determined in blood. Rats receiving the ISP diet demonstrated increased activity of antioxidant enzyme activity and nitrite/nitrate content. In addition, the increase in LPO seen in rats subjected to MI was significantly mitigated when the ISP diet was given. These findings suggest a nutritional approach of using a soy-based diet for the prevention of oxidative-stress-related diseases such as heart failure.
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