INTRODUCTION

Coronary heart disease (CHD) is the leading cause of death in the United States and with one exception has been every year since 1900. CHD is also the most expensive disease in terms of costs, hospital stays, doctor visits, rehabilitation, emergency room visits as well as preventative measures.

Women often fear breast cancer more, but CHD is the number one cause of death. For women CHD occurs approximately 10 years later than in men but it is often fatal, 67% percent of the time death is the first symptom. Once a woman reaches menopause the risk of heart disease and stroke rise dramatically with age.

BLOOD LIPIDS

In October 1999 the FDA approved a new health claim for soy protein and coronary heart disease. Specifically, the claim states that “diets low in saturated fat and cholesterol that include 25 grams of soy protein a day may reduce the risk of heart disease.” The legislation authorizing health claims requires significant scientific evidence and scientific consensus before approving any claims for foods relative to reducing the risk of a disease. The agency analyzed the results of nearly 40 clinical trials before granting the claim.

The American Heart Association endorses eating soy foods to lower cholesterol and triglycerides and the risk of heart disease. Specifically, soy protein preferentially lowers LDL cholesterol and lowers total cholesterol, two of the major risk factors in CHD. Moreover, it does not lower HDL cholesterol as many interventions do.

A landmark meta-analysis (Anderson, et al.1995) was conducted that evaluated the affect of soy protein intake on serum lipids. The study, published in the New England Journal of Medicine, analyzed the results of 38 controlled clinical trials. The results showed that ingestion of soy protein was associated with significant declines in total cholesterol, LDL cholesterol and triglycerides.

More recently Zhuo and co-workers (2004) conducted a meta-analysis of 8 clinical trials to determine the affect of soy isoflavones, independent of soy protein intake, on blood LDL cholesterol concentration. The results of the analysis were two fold. First, decreases in serum LDL cholesterol were greater in hypercholesterolemic subjects versus normocholesterolemic subjects confirming Anderson’s findings. . Second, with identical soy protein intake (50 grams/day), high isoflavone intake led to significantly (P < 0.001) greater decreases in serum LDL cholesterol than low isoflavone intake. Zhuo concluded that isoflavones have LDL cholesterol-lowering effects independent of soy protein.

It’s important to note the results of these studies. The Anderson study focused on soy protein and the FDA claim for heart health is specifically for soy protein. The Zhuo study concluded that isoflavones have LDL cholesterol-lowering effects independent of soy protein. This means that consumers who need to lower their risk for heart disease are likely best served by foods or supplements that contain both soy protein and isoflavones versus isoflavone supplements alone. However, FDA recognizes only soy protein for its approved health claim.

Consumption of soy protein does not appear to have a hypocholesterolemic effect in adults with low or normal cholesterol levels. There is no evidence to suggest that soy consumption could cause dangerously low levels of cholesterol.

BLOOD VESSEL HEALTH

Recent data indicates that soy has other beneficial effects on the cardiovascular system in addition to improving the lipid profile. Several studies suggest that isoflavones and isoflavone-rich soy protein favorably affect blood vessel function (Nestel et al., 1997; van der Schouw et al., 2002; Nestel, 2003; Squadrito et al., 2003; Steinberg et al., 2003).

Nestel et al. (1997) performed a placebo-controlled, crossover trial using isoflavone tablets (80 mg isoflavone of which 45 mg was genistein) and placebo tablets in which systemic arterial compliance was measured within the main conduit arteries. Isoflavones significantly improved systemic arterial compliance. The placebo had no effect on systemic arterial compliance while the isoflavone group experienced a 26% improvement. The authors speculated that the smooth muscle layer within the vessel wall may be influenced by endothelial cell events and that soy isoflavones stimulate endothelial-related arteriolar relaxation.

In a trial (Steinberg et al., 2003) designed to evaluate the effect of isolated soy protein compared to caseinate on plasma lipoproteins and endothelial function in postmenopausal women soy protein was shown to significantly (P < 0.05) increase flow-mediated dilation compared to baseline (9.4 ± 1.8% versus 5.3 ± 1.2%) and compared to caseinate (9.4 ± 1.8% vs. 4.9 ± 1.5%). In a second study 28 women were enrolled in a randomized, double-blind, crossover study and they consumed 25 grams of 3 protein products/day for 6 weeks each with intervening washout periods (Cuevas et al., 2003). The products were isolated soy protein with isoflavones, ethanol-washed isolated soy protein with trace isoflavones, and total milk protein. The results indicated that the postocclusion peak flow velocity of the brachial artery was significantly (P = 0.03) lower after treatment with isolated soy protein with isoflavones than after treatment with total milk protein. This result is consistent with a vasodilatory response.

ANTIOXIDANT EFFECTS

Soy isoflavones have antioxidant activities in vitro and have been reported to contribute to increasing LDL ex vivo oxidation resistance. In two studies, investigators found that 56 and 60 mg of soy isoflavones, respectively, decreased F2 –isoprostane concentrations (an in vivo marker of oxidation) and inhibited in vitro LDL oxidation (Wiseman et al., 2000, Nestel et al., 1997).

PARTICLE SIZE AND HOMOCYSTEINE LEVELS

Other studies have reported beneficial effects of soy or soy isoflavones on LDL particle size (Deroches et al., 2004) and homocysteine levels (Nagata et al., 2003). In a study conducted among 36 moderately hypercholesterolemic men and women consumption of soy protein was associated with a larger LDL peak particle size relative to animal protein (Desroches et al., 2004). The shift in LDL particle size represents a less atherogenic pattern. This effect was associated with soy protein and was independent of the isoflavone component. Elevated blood homocysteine levels are an independent risk factor for cardiovascular disease and a recent cross-sectional study of the relationship between soy intake and homocysteine levels indicated that increased soy intake was associated with lower blood homocysteine levels (Nagata et al., 2003).

While a number of these areas clearly require more investigation there is growing evidence that soy has significant positive effects on cardiovascular health. It’s possible to argue that although the improvements in lipid profiles, while important, may not be the benefit of greatest value.

REFERENCES
1. Anderson JW, Johnstone, BM, Cook-Newell ME. Meta-analysis of the effects of soy protein intake on serum lipids. N Engl J Med 1995; 333: 276-282
2. 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 2004; 134:2395-2400
3. Nestel PJ, Yamashita T, Sasahara T, Pomeroy S, Dart A, Komesaroff P, Owen A, Abbey M. Soy isoflavones improve systemic arterial compliance but not plasma lipids in menopausal and perimenopausal women. Arterioscler Thromb Vasc Biol 1997; 17:3392-3398
4. Van der Schouw YT, Pijpe A, Lebrun CEI, Bots ML, Peeters PHM, van Staveren WA, Lamberts SWJ, Grobbee DE. Higher usual dietary intake of phytoestrogens is associated with lower aortic stiffness in postmenopausal women, Arterioscler Thromb Vasc Biol 2002; 22:1316-1322.
5. Nestel P. Isoflavones: their effects on cardiovascular risk and functions. Curr Opin Lipidol 2003; 14:3-8
6. Squadrito F, Altavilla D, Crisafulli A, Saitta A, Cucinotta D, Morabito N, D’Anna R, Corrado F, Ruggeri P, Frisina N, Squadrito G. Effect of genistein on endothelial function in postmenopausal women: a randomized, double-blind, controlled study. Am J Med 2003; 114:470-476
7. Steinberg FM, Guthrie NL, Villablanca AC, Kumar K, Murray MJ. Soy protein with isoflavones has favorable effects on endothelial function that are independent of lipid and antioxidant effects in healthy postmenopausal women, Am J Clin Nutr 2003; 78:123-30
8. Ceuvas AM Irribarra VL, Castillo OA, Yanez MD, Germain AM. Isolated soy protein improves endothelial function in postmenopausal hypercholesterolemic women. Eur J Clin Nutr 2003; 57:889-894.
9. Wiseman H, O’Reilly JD, Adlercreutz H, Mallet AI, Bowey EA, Rowland IR, Sanders TAB. Isoflavone phytoestrogens consumed in soy decrease F2-isoprostane concentrations and increase resistance of low-density lipoprotein to oxidation in humans. Am J Clin Nutr 2000; 72:395-400
10. 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; 134:574-9
11. Nagata C, Shimizu H, Takami R, Hayashi M, Takeda N, Yasuda K. Soy product intake is inversely associated with serum homocysteine level in premenopausal Japanese women. J Nutr 2003; 133:797-800

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