Healthnotes Newswire (June 15, 2000)—Parts one through four of this series examined the health effects of soybeans, which are rich in isoflavones. Isoflavones are considered “phytoestrogens” because they are structurally similar to estrogen and may have estrogen-like effects in the body. Compared to human and pharmaceutical estrogens, the estrogenic activity of isoflavones is quite weak.¹ Evidence suggests that phytoestrogens from soy confer protection against a wide array of conditions, including heart disease, osteoporosis, prostate cancer, and some symptoms of menopause. Other constituents in soy may also be important for the prevention and treatment of heart disease.

Foods containing soy protein are widely recognized for their ability to lower blood cholesterol levels, a well accepted indicator of heart disease. These foods include tofu, tempeh, and soy milk. In November of 1998, the U.S. Food and Drug Administration proposed allowing the following health claim on food labeling: “Diets low in saturated fat and cholesterol that include 25 grams (almost one ounce) of soy protein per day may reduce the risk of heart disease.”² While this landmark position suggests that soy supplementation might benefit everyone, the cardiovascular effects of soy appear to be more significant in people who already have elevated cholesterol levels, and the benefits for people with healthy cholesterol levels are less certain.

A double-blind trial, published last month in the American Journal of Clinical Nutrition, found that soy supplementation, in amounts as low as 20 grams per day, effectively improved the blood cholesterol profile after only six weeks.³ Eighty-one men with moderately elevated cholesterol levels (220–300 mg per deciliter—a normal cholesterol level is less than 200 mg per deciliter) were given 20 grams, 30 grams, 40 grams, or 50 grams per day of soy protein or placebo for six weeks. All study participants had been previously placed on a cholesterol-lowering diet (the National Cholesterol Education Program Step 1 diet) for three weeks. In those supplementing with soy, the cholesterol profile was improved (by about 2.6%) beyond levels achieved with diet alone.

This good news may be especially important to people who have unsuccessfully tried to lower their cholesterol levels with one of the commonly prescribed cholesterol-lowering “statin” drugs (e.g., lovastatin [Mevacor®], simvastatin [Zocor®], and atorvastatin [Lipitor®]). In a double-blind trial published last year in the British Journal of Nutrition, 21 patients with severely elevated blood cholesterol levels took a soy protein drink (providing 35 grams of protein per day) or placebo (cow’s milk protein) daily for four weeks.⁴ Each of these patients had a history of resistance to or intolerance of statin-type cholesterol-lowering drugs. At the end of four weeks, the group receiving soy supplementation experienced a 6.5–7.4% reduction in total cholesterol levels.

Evidence of a cholesterol-lowering effect of soy protein supplements was well summarized in a 1995 analysis of 38 controlled clinical trials.⁵ When analyzing these trials as a group, the following trends were observed for soy supplementation: total cholesterol dropped an average of 9.3% compared to initial levels; LDL (“bad”) cholesterol dropped an average of 12.9%; and triglycerides decreased an average of 10.5%.

Does Soy Help Everyone?

Current evidence suggests that soy supplementation is likely to confer benefits on people who have elevated blood cholesterol levels;^{3 4 5 11 12 13 14} however, its effects on people with normal cholesterol levels have been inconsistent.^{6 7 8 9} For heart disease prevention, soy supplementation may be more beneficial for women than for men. In a double-blind trial, published last year in the journal Menopause, 51 menopausal women with normal cholesterol levels were given either 20 grams of soy protein (providing 34 mg isoflavones) once daily, the identical daily dose divided in two servings, or a 20-gram carbohydrate placebo.¹⁰ When following either soy supplementation program, significant reductions from initial cholesterol levels were achieved for both total cholesterol (6% lower) and LDL cholesterol (7% lower). Additional benefits of the twice-daily supplementation program included a lowering of diastolic blood pressure by 5 millimeters of mercury (the lower number on the blood pressure reading) and a reduction in symptoms of menopause.

However, a new trial, published this month in the American Journal of Cardiology, found no beneficial effect on cholesterol or blood pressure from an isoflavone supplement (extracted from soy) when taken by postmenopausal women with normal cholesterol levels.¹¹ In this double-blind trial, 20 postmenopausal women followed a cholesterol-lowering diet for three weeks. The trial participants were then given either 80 mg per day of soy isoflavones or placebo for eight weeks. Although total and LDL cholesterol levels dropped 6 to 8% below initial values in both groups, HDL (“good” or heart-protective) cholesterol dropped as well. More important, these reductions were attributed to the diet change alone. Women taking the isoflavone supplement apparently experienced no additional cholesterol-lowering benefit.

While the benefit of soy supplementation for postmenopausal women with normal cholesterol levels is uncertain, it is clearer that men with normal cholesterol levels are not likely to experience a preventive, cholesterol-lowering effect. For example, in a randomized, controlled trial, published last January in the European Journal of Clinical Nutrition, 42 healthy men were given diets similar in terms of caloric content, fat content, and fiber content, and either protein from lean meat or tofu for one month.¹² Total cholesterol and triglyceride levels were lower in men eating the tofu diet as compared with men eating the lean meat diet. While this in itself is a positive result, HDL cholesterol was also significantly lower in men eating the tofu diet. The reasons for this unexpected effect on HDL are probably gender-based and may relate to estrogen-like effects of whole soy rich in isoflavones, which can beneficially influence HDL in women,¹³ but not in men. This theory has not been proven.

Soy protein supplementation may be most effective at lowering cholesterol in people with the highest levels of blood cholesterol. In a double-blind trial, published last year in the Archives of Internal Medicine, 156 men and women with elevated total cholesterol and LDL levels were given either placebo or 25 grams of soy protein (containing either 3, 27, 37, or 62 mg of isoflavones) for nine weeks.¹⁴ Each participant followed the National Cholesterol Education Program Step 1 diet prior to being given one of the four daily doses of soy protein or the placebo. The participants with the highest initial blood levels of LDL cholesterol (greater than 166 mg per deciliter—normal is less than 140) had the greatest reductions in total cholesterol (9% lower) and LDL cholesterol (10% lower) when taking the soy protein supplement with the highest isoflavone content. People with the highest cholesterol levels also experienced a lesser reduction in total and LDL cholesterol (both 8% lower) when taking the 37-mg isoflavone soy supplement.

How Does It Work?

There are several current theories about how soy products lower cholesterol.¹⁵ Some propose that soy decreases cholesterol absorption; others suggest an alteration of hormone balance that leads to increased clearance of cholesterol from the blood and a decrease in the cholesterol content of liver secretions (the liver is responsible for the metabolism and breakdown of cholesterol).

As the Archives of Internal Medicine trial emphasized, the isoflavone content of soy products may be a key factor. People consuming soy supplements with higher isoflavone content are more likely to experience greater reductions in both total and LDL cholesterol. However, the new American Journal of Cardiology trial,¹¹ as well as evidence from previous trials,¹⁶ suggests that isoflavones alone are not the whole story: by themselves, they are unlikely to account for the cholesterol-lowering properties of soy. Some combination of soy protein, isoflavones, and other soy constituents may be necessary to achieve the desired cholesterol-lowering effects.