한국콩연구회

Soy May Favorably Affect Non-Traditional Risk Factors For Coronary Heart Disease 

ark Messina, PhD

The fact that soyfoods can play an important role in heart-healthy diets is fairly self-evident.  They provide high quality protein,1 are low in saturated fat, and high in polyunsaturated fat.2  Soy protein lowers blood LDL-cholesterol levels, an attribute formally recognized by the Food and Drug Administration in 1999,3 and may also lower blood pressure4 and triglyceride levels.5  Elevated cholesterol and blood pressure, along with smoking and diabetes, are well-recognized risk factors for coronary heart disease (CHD).  But as Freeman and Buckley note in their excellent article in this issue of the newsletter, 15% to 20% of patients with CHD have no traditional risk factors.6  Consequently, identifying risk factors that improve the clinician’s ability to predict risk of future coronary events continues to be a subject of considerable interest.  A number of potential CHD risk factors, as discussed in the lead article, are being evaluated.

There is both clinical direct and indirect epidemiologic evidence that soyfoods favorably affect CHD risk, independent of effects on blood pressure and cholesterol.  In regard to the latter, a prospective study involving nearly 65,000 postmenopausal women from Shanghai found that soy protein intake was associated with an 86% reduction in the risk of non-fatal myocardial infarction.7  In agreement, a prospective study involving 40,462 Japanese participants (40-59 years old, without cardiovascular disease or cancer at baseline) found that when comparing women with frequent (³5x/week) vs. infrequent (≤2x/week) soy consumption, the multivariable hazard ratios were 0.64, 0.55 and 0.31 for risk of the incidence of cerebral infarction, myocardial infarction, and CHD mortality, respectively.8  The magnitude of the protective effects associated with soy consumption in these studies is far beyond that which could be due to any expected effect of soy on blood pressure and cholesterol alone.

One of the non-traditional risk factors discussed by Freeman and Buckley, carotid intima-media thickness (IMT), may be favorably affected by soy intake.  In support of this suggestion is a cross-sectional study involving 406 Chinese adults ages 40-65 years old (134 males, 272 females), without confirmed relevant diseases, which found that soyfood intake was inversely related to bifurcation intima-media thickness, although the association was more apparent in men than women.9  Also, in a three-year clinical trial, Hodis et al.10 found that in comparison to women consuming 25 g/d milk protein, cartoid IMT increased 16% less in postmenopausal women consuming 25 g/d isoflavone-rich soy protein.  The difference between groups was not statistically significant; however, subanalysis showed that among women approximately 50-55 years of age, carotid IMT decreased by 68% in the soy vs. the milk group–a difference that was statistically significant.

No information on the mechanism by which carotid IMT was reduced can be gleaned from either of the two previously cited studies, but one mechanism may be an improvement in arterial health.  There is substantial evidence that soy isoflavones improve endothelial function as measured by flow mediated dilation in postmenopausal women with impaired endothelial health.11

Research has also been conducted on the effects of soy on C-reactive protein (CRP), a measure of inflammation, which was highlighted by Freeman and Buckley as a promising non-traditional CHD risk factor.  However, as pointed out by a review published several years ago, the results of clinical trials evaluating the effects of soy on this endpoint have been conflicting.12  Furthermore, trials published subsequent to this review have not shown that soy reduces CRP levels.13, 14

Another risk factor under investigation is periodontal disease.  The results of the only study identified evaluating the effects of soy on periodontal disease are intriguing.  The participants for this study were 3,956 Japanese female students, aged 18 to 22 years, who were taking a dietetic course.  Among the group overall, the prevalence of periodontal disease was 8.0 %.15  Intake of total soy products and tofu was independently associated with a decreased prevalence of periodontal disease; multivariate odds ratios when comparing the highest with the lowest quintile were 0.68 (P for trend = 0.01) and 0.68 (P for trend = 0.004), respectively.  Periodontal disease was defined as present when a subject reported diagnosis of the disorder by a dentist. The results were adjusted for cigarette smoking, tooth brushing frequency, region of residence, and body mass index.

Finally, soy intake may favorably affect several possible non-traditional risk factors not discussed in the article by Freeman and Buckley.  For example, soy has been shown in clinical trials to reduce LDL-cholesterol oxidation,16 LDL-C particle size,17 systematic arterial compliance18 and to decrease platelet thromboxane A2 receptor density (and therefore possibly clot formation).19  However, research into the effect of soy on these markers is too limited and/or conflicting to reach any definitive conclusions at this time.

In summary, soy favorably affects at least one established CHD risk factor, elevated cholesterol, and may affect another, elevated blood pressure.  In addition, there is intriguing but speculative evidence that soy may favorably affect one or more non-traditional risk factors.

REFERENCES

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Slavin M, Kenworthy W, Yu LL: Antioxidant properties, phytochemical composition, and antiproliferative activity of Maryland-grown soybeans with colored seed coats. J Agric Food Chem 2009, 57(23):11174-11185.

Food labeling: health claims; soy protein and coronary heart disease. Food and Drug Administration, HHS. Final rule. Fed Regist 1999, 64(206):57700-57733.

Dong JY, Tong X, Wu ZW, Xun PC, He K, Qin LQ: Effect of soya protein on blood pressure: a meta-analysis of randomised controlled trials. Br J Nutr 2011, 106(3):317-326.

Zhan S, Ho SC: Meta-analysis of the effects of soy protein containing isoflavones on the lipid profile. Am J Clin Nutr 2005, 81(2):397-408.

Smith SC, Jr.: Current and future directions of cardiovascular risk prediction. Am J Cardiol 2006, 97(2A):28A-32A.

Zhang X, Shu XO, Gao YT, Yang G, Li Q, Li H, Jin F, Zheng W: Soy food consumption is associated with lower risk of coronary heart disease in Chinese women. J Nutr 2003, 133(9):2874-2878.

Kokubo Y, Iso H, Ishihara J, Okada K, Inoue M, Tsugane S: Association of dietary intake of soy, beans, and isoflavones with risk of cerebral and myocardial infarctions in Japanese populations: the Japan Public Health Center-based (JPHC) study cohort I. Circulation 2007, 116(22):2553-2562.

Zhang B, Chen YM, Huang LL, Zhou XX, Chen CG, Ye YB, Su YX: Greater habitual soyfood consumption is associated with decreased carotid intima-media thickness and better plasma lipids in Chinese middle-aged adults. Atherosclerosis 2008, 198(2):403-411.

Hodis HN, Mack WJ, Kono N, Azen SP, Shoupe D, Hwang-Levine J, Petitti D, Whitfield-Maxwell L, Yan M, Franke AA et al: Isoflavone soy protein supplementation and atherosclerosis progression in healthy postmenopausal women: a randomized controlled trial. Stroke 2011, 42(11):3168-3175.

Li SH, Liu XX, Bai YY, Wang XJ, Sun K, Chen JZ, Hui RT: Effect of oral isoflavone supplementation on vascular endothelial function in postmenopausal women: a meta-analysis of randomized placebo-controlled trials. Am J Clin Nutr 2010, 91(2):480-486.

Messina M, Lane B: Soy protein, soybean isoflavones, and coronary heart disease risk: Where do we stand? Future Lipidology 2007, 2:55-74.

Riesco E, Choquette S, Audet M, Lebon J, Tessier D, Dionne IJ: Effect of exercise training combined with phytoestrogens on adipokines and C-reactive protein in postmenopausal women: a randomized trial. Metabolism 2012, 61(2):273-280.

Liu ZM, Ho SC, Chen YM, Ho YP: The effects of isoflavones combined with soy protein on lipid profiles, C-reactive protein and cardiovascular risk among postmenopausal Chinese women. Nutr Metab Cardiovasc Dis 2012, 22(9):712-719.

Tanaka K, Sasaki S, Murakami K, Okubo H, Takahashi Y, Miyake Y: Relationship between soy and isoflavone intake and periodontal disease: the Freshmen in Dietetic Courses Study II. BMC Public Health 2008, 8(1):39.

Jenkins DJ, Kendall CW, Connelly PW, Jackson CJ, Parker T, Faulkner D, Vidgen E: Effects of high- and low-isoflavone (phytoestrogen) soy foods on inflammatory biomarkers and proinflammatory cytokines in middle-aged men and women. Metabolism 2002, 51(7):919-924.

Desroches S, Mauger JF, Ausman LM, Lichtenstein AH, Lamarche B: Soy protein favorably affects LDL size independently of isoflavones in hypercholesterolemic men and women. J Nutr 2004, 134(3):574-579.

Teede HJ, McGrath BP, DeSilva L, Cehun M, Fassoulakis A, Nestel PJ: Isoflavones reduce arterial stiffness: a placebo-controlled study in men and postmenopausal women. Arterioscler Thromb Vasc Biol 2003, 23(6):1066-1071.

Garrido A, De la Maza MP, Hirsch S, Valladares L: Soy isoflavones affect platelet thromboxane A2 receptor density but not plasma lipids in menopausal women. Maturitas 2006, 54(3):270-276.

About the Author

Mark Messina, PhD, is the co-owner of Nutrition Matters, Inc., a nutrition consulting company, and is an adjunct professor at Loma Linda University. His research focuses on the health effects of soyfoods and soybean components. He is chairman of The Soy Connection Editorial Board and executive director of the Soy Nutrition Institute.

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