Tofu, Other Isoflavone-Rich Foods May Cut Heart Disease Risk

Batya Swift Yasgur MA, LSW

April 10, 2020

Regular consumption of tofu and other plant-based foods that are rich in isoflavones predicts a reduced long-term risk for fatal or nonfatal coronary heart disease (CHD), especially for younger women, suggests a pooled analysis of data from three major prospective cohort studies.

Among the more than 200,000 participants across the three studies, followed clinically for 4.8 million person-years, those who consumed tofu more than once a week showed an 18% lower (P = .005) adjusted risk for CHD events than those who ate tofu less than once a month.

The corresponding risk reduction was 13% for consumption of isoflavone-risk foods in general; no similar benefit was observed for intake of soy milk.

The association between tofu consumption and reduced CHD risk was largely driven by a benefit in younger, premenopausal women and postmenopausal women who were not taking hormones.

"The take-home message is that prevention is the cornerstone of public health, and clinicians should encourage their patients who are at elevated risk of developing heart disease to consider healthy plant-based diets, for which tofu and other soy products can be really good components," Qi Sun, MD, ScD, Brigham and Women's Hospital and Harvard Medical School, Boston, told | Medscape Cardiology.

Sun is lead author on the pooled analysis of participants in the Nurses' Health Study (NHS), Nurses' Health Study II (NHS II), and Health Professionals Follow-up Study (HPFS), published online March 23 in Circulation.

The findings "provide some additional value from data accrued from highly selected populations that consuming isoflavone-containing foods, particularly on a background of a heart-healthy dietary pattern, reduces the risk of developing heart disease, Robert H. Eckel, MD, University of Colorado Anschutz Medical Campus, Aurora, told | Medscape Cardiology.

Their take-home message for clinicians is to "emphasize a heart-healthy lifestyle, including heart-healthy dietary pattern, physical activity, and smoking cessation at least briefly in every patient encounter," said Eckel, who was not involved in the study.

More Than Just Nutrition

"The question of whether soy intake is healthy or not is pretty old, and before our study, there was already much research dedicated to understanding the metabolism of isoflavones and the health effect of soy intake on risk markers," said Sun when interviewed.

"What really motivated our study is that more and more people have started realizing that our diet can have a significant impact on the environment, and that switching from animal-product-dense diets to healthy plant-based diets can not only improve human health, but also the health of our earth," he continued.

"For plant-based diets, such as vegetarian and vegan diets, tofu and other soy products can function as an important source of protein," Sun observed. Yet, he added, whether tofu and other soy and isoflavone-rich foods are beneficial to heart health is still controversial.

The study population was made up of 74,241 women from the NHS, conducted from 1984 to 2012; 94,233 women from NHS II, conducted from 1991 to 2013; and 42,226 men from HPFS, conducted from 1986 to 2012.

All participants were required to be free of cardiovascular disease (CVD) and cancer at baseline.

Every 2 to 4 years, participants filled out validated food-frequency questionnaires (FFQ), which included a question on soy milk consumption since1998 in the NHS, since 1999 in NHS II, and since 2002 in HPFS.

Based on the FFQ responses, the researchers derived an alternative healthy-eating index (AHEI), which summarized intake of 11 foods or nutrients: vegetables, fruits, whole grains, sugar-sweetened beverages and fruit juice, nuts and legumes, red meat and processed meat, trans fats, long-chain n-3 fatty acids, polyunsaturated fats, sodium, and alcohol.

For the current study, tofu and soy milk were excluded from AHEI calculations.

Every 2 years, the researchers sent out follow-up questionnaires to collect data on demographics, anthropometrics, and lifestyle factors (for example, body weight, cigarette smoking, physical activity, medication, and supplement use), menopausal and postmenopausal status, any postmenopausal hormone therapy (HT), and personal and family history of myocardial infarction (MI), diabetes, hypertension, and hypercholesterolemia.

Tofu, But Not Soy Milk

There were 8359 documented incident cases of CHD — nonfatal MI or death from CVD — over a follow-up period of 4,826,122 person-years. At the midpoint of follow-up, 24.1% of participants were consuming more than one serving of tofu per week.

Higher isoflavone intake was associated with greater consumption of vegetables, more exercise, and higher AHEI score in all three of the cohorts. Similarly, participants who frequently ate tofu were more likely to be physically active, have a higher AHEI score, consume more fruits and vegetables, and have lower intakes of meat and trans fats.

Isoflavone intake was inversely associated with incident CHD in an adjusted analysis that compared the highest with the lowest isoflavone-intake quintiles (pooled hazard ratio [HR], 0.87; 95% CI, 0.81 - 0.94; = .008).

The multivariate adjustment included AHEI score, age, sex, ethnicity, socioeconomic status, partner's educational level, smoking status, alcohol intake, physical activity level, multivitamin use, aspirin use, history of hypertension and hypercholesterolemia, family MI history, menopausal status, postmenopausal hormone use, oral contraceptive use, body mass index, and estimated total energy intake.

Also observed was a significant inverse association between consumption of tofu and incident CHD (pooled HR, 0.82; 95% CI, 0.70 - 0.95; P for trend = .005; no such significant trend was seen for soy milk.

Soy milk and tofu have different nutritional profiles, the authors note, perhaps because "unlike tofu, soy milk may contain added sugar, emulsifiers, and other constituents which may mask the protective effects of isoflavones on CHD risk, to a certain extent."

Possible Estrogenic Effects

On further analyses, the benefits of greater tofu consumption (at least one serving per week vs none) was largely driven by an inverse association among premenopausal women and postmenopausal women not using HT, but not in postmenopausal women on HT (interaction P = .002):

  • Premenopausal women: HR, 0.45; 95% CI, 0.16 - 1.23; P for trend = .02)

  • Postmenopausal women never using HT: HR, 0.51; 95% CI, 0.26 - 1.02; P for trend = .03)

  • Postmenopausal women using HT: HR, 1.04; 95% CI, 0.76 - 1.42; P for trend = .87).

"Isoflavones are known to mimic estrogens and exert weak estrogenic effects," Sun observed for | Medscape Cardiology. "In animal and human experiments, we know that isoflavones and/or their metabolites are potent antioxidants, improve blood lipid profiles, alleviate insulin resistance, and reduce inflammation."

The current study "explains a mechanism behind much of [the investigators'] previous work indicating that there are no safe animal products for consumption, and that vegetable protein, particularly in the form of soy with its isoflavones, decreases cardiac events," cardiologist and celebrated vegan Kim Allan Williams Sr., MD, Rush University Medical Center, Chicago, told | Medscape Cardiology.

Williams, who was not involved with the pooled analysis, said that the "benefits of soy are wide-ranging, but reduction of events with soy instead of animal protein, if widespread use occurs, could reduce cardiac events enough to remove heart disease as the number one killer of Americans, which it has been for the past 101 years."

The study was funded by the National Institutes of Health. Sun and coauthors, Eckel, and Williams report no relevant financial relationships.

Circulation. Published online March 23, 2020. Full text

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