Soy consumption, adhesion molecules, and pro-inﬂammatory cytokines: a brief review of the literature Kristen M Beavers, Satya S Jonnalagadda, and Mark J Messina Given the interest in the vascular eﬀects of both soyfoods and soy isoﬂavones, the purpose of this short review is to evaluate clinical trials that have examined the eﬀects of isoﬂavone-rich soy products on the novel cardiovascular risk factors, cellular adhesion molecules, and pro-inﬂammatory cytokines. A total of 14 randomized clinical studies were assessed. From the data evaluated, evidence suggests that neither soyfoods nor soy isoﬂavones aﬀect IL-6 or TNF-a expression. In contrast, the eﬀects of soy on cellular adhesion molecules are mixed. Study design characteristics possibly contributing to the inconsistent data are discussed and recommendations for future research in this area are presented. © 2009 International Life Sciences Institute INTRODUCTION The soybean is a versatile legume that contains high- quality protein, minimal saturated fat, and is an essen- tially unique dietary source of isoﬂavones 1 – a group of diphenolic compounds classiﬁed as phytoestrogens. Isoﬂavones bind to both estrogen receptors, although preferentially to estrogen receptor beta (ERb), 2 and in people who regularly consume soyfoods, serum isoﬂa- vone levels reach the low micromolar range. 3 In soybeans, the three isoﬂavones genistein, daidzein, and glycitein comprise approximately 50%, 40%, and 10% of total isoﬂavone content, respectively. 4 Of the three isoﬂavones, genistein has received the most attention. In recent years these foods have been studied exten- sively for their ability to reduce the risk of several chronic diseases, particularly cardiovascular disease (CVD). To date, more than 100 clinical studies have examined the eﬀects of soy protein on blood cholesterol levels. Although initial estimates 5 of the hypocholesterolemic eﬀects of soy protein are now known to be too high, recent meta-analyses indicate soy protein directly lowers blood low-density-lipoprotein cholesterol (LDL-C) levels by 3–5%. 6,7 Over a period of many years, even this modest reduction can, in theory, reduce coronary heart disease (CHD) risk by as much as 10%. 8 Interestingly, in animal models, both soy protein and soybean isoﬂavones have been shown to reduce the devel- opment of atherosclerosis independent of eﬀects on LDL- C. 9,10 Further, several Asian epidemiologic studies have found higher soy intake to be associated with substantial reductions (30–86%) in the risk of developing CVD and/or having coronary events. 11,12 Such protective eﬀects are far beyond that which can be attributable to choles- terol lowering alone, even when considering the addi- tional reduction in cholesterol that occurs when soyfoods displace foods high in saturated fat from the diet. These epidemiologic observations coupled with evidence from animal models have led to the concept that soy favorably aﬀects one or more of the lipid-independent CVD risk factors. In this regard, there is evidence that soy protein lowers blood pressure 13 and that soybean isoﬂavones enhance endothelial function, as measured by changes in ﬂow mediated dilation (FMD) and systematic arterial compliance, although the data are inconsistent. 14 Several mechanisms have been proposed by which isoﬂavones might improve endothelial function, these include Aﬃliations: KM Beavers is with the Department of Health, Human Performance, and Recreation, Baylor University, Waco, Texas, USA. SS Jonnalagadda is with the General Mills Bell Institute of Health and Nutrition, Minneapolis, Minnesota, USA. MJ Messina is with Nutrition Matters, Inc., Port Townsend, Washington, USA. Correspondence: KM Beavers, Department of Health, Human Performance, and Recreation, Baylor University, One Bear Place # 97304, Waco, TX 76798-7313, USA. E-mail: kristen_beavers@baylor.edu, Phone: +1-254-710-3243, Fax: +1-254-710-3527. Key words: adhesion molecules, cardiovascular disease, cytokines, inﬂammation, isoﬂavones, soy Special Article doi:10.1111/j.1753-4887.2009.00191.x Nutrition Reviews® Vol. 67(4):213–221 213