Oct. 1, 1999 WINSTON-SALEM, N.C. -- The cholesterol-lowering effect of soy depends on the amount of isoflavones --plant estrogens--in the soy, according to a study at Wake Forest University Baptist Medical Center. Soy high in isoflavones can lead to dramatic drops in cholesterol.
Soy from which the isoflavones had been extracted does not lower cholesterol, nor does a relatively low dose of isoflavones in soy protein, said John R. Crouse, III M.D., writing in the current Archives of Internal Medicine.
"Our study does not allow us to define which of the many component isoflavones in soy protein may lower cholesterol," said Crouse, professor of internal medicine (endocrinology and metabolism) and public health sciences.
He conducted a nine-week study that assigned participants to eat soy protein containing one of four amounts of isoflavones, ranging from a low of 3 milligrams of isoflavones (most of the isoflavones had been extracted) to a high of 62 milligrams, or a milk protein placebo.
The results were dramatic in the 62 milligram group. In just nine weeks, the low-density lipoprotein (LDL) cholesterol levels dropped by 10 percent in those patients whose LDL levels were greater than 164 mg/dl, a moderately high level. LDL is the bad cholesterol that doctors believe elevates the risk of heart disease. In the same group, total cholesterol dropped by 9 percent.
When all patients who got the 62 milligrams dose were consolidated (including those whose LDL was closer to normal), LDL cholesterol still dropped by 6 percent in the nine weeks, and total cholesterol dropped by 4 percent. All of these declines were statistically significant.
Patients in the high LDL group who got soy containing 37 milligrams of isoflavones also showed steep drops of 8 percent in both LDL and total cholesterol, but when all the patients who got 37 milligrams were grouped together, the results were not statistically significant.
Patients who got 27 milligrams of isoflavones and those who got the soy with only 3 milligrams of isoflavones (alcohol-washed soy) showed little decline in either total or LDL cholesterol.
There was evidence of what doctors call a "dose-response relationship" --as the amount of isoflavones increased, the cholesterol-lowering effect got stronger. "The dose-response relationship raises the possibility that soy protein with higher amounts of isoflavones might have even greater cholesterol lowering effects," Crouse said
And, as isoflavone content increased, blood pressure decreased among the female participants. High blood pressure is a separate risk factor for heart disease.
Crouse and his colleagues noted other studies that suggested that people in Asian countries consume 30 to 50 times more soy than in Western countries. People in those countries have a low prevalence of breast and uterine cancer and cardiovascular diseases.
Almost a thousand times as much isoflavones is found in the urine of people in Asian countries than in American populations. "Isoflavones are particularly good candidates for the cardioprotective effects of soy because of their many chemical and biological similarities to mammalian estrogen," he said.
Crouse said that while the cholesterol lowering properties of soy have been widely accepted, "the active ingredient had not been previously been identified." Speculation previously has ranged from the soy protein itself to a variety of other ingredients contained in soy.
"It is now evident that isoflavones are responsible for the cholesterol-lowering effect," he said. "How the isoflavones work is another question. There is some evidence that they need the soy protein to work since other research has shown that isoflavones alone do not lower cholesterol."
Studies at Wake Forest and elsewhere have found that the effects of estrogen and isoflavones on cholesterol are parallel in monkeys and people. In monkeys, studies have shown that soy containing isoflavones reduces atherosclerosis, "and there is considerable evidence suggesting the same is true for estrogens in human beings," Crouse said.
The study was supported by Protein Technologies International and the General Clinical Research Center at Wake Forest, which in turn is supported by the National Institutes of Health.
The team also included Timothy Morgan, Ph.D., James G. Terry, M.S., Julie Ellis, M.P.H., Mara Vitolins, Dr. P.H. and Gregory L. Burke, M.S., M.S.
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