Effect of Equol Supplementation on Arterial Stiffness and Cognition in Healthy Volunteers

Prior treatment

• Women on estrogen replacement therapy

Other illness

• Individuals who have allergy or intolerance to soy isoflavones.
• Individuals with stroke, neurological disorders, bipolar disease whether or not under medical treatment, cancer treatment in the past 6 months, head trauma or other condition which is not appropriate for the study (e.g., contraindication to magnetic resonance imaging (MRI)).
• Individuals with heart failure
• Individuals with heart attack or coronary intervention in the past 6 months
• Individuals with carotid endarterectomy or peripheral artery disease
• Individuals currently undergoing treatment for pulmonary embolism or deep vein thrombosis
• Individuals with inflammatory bowel diseases
• Women with a past or family history of breast cancer.\*1
• Individuals with Quick Dementia Rating System (QDRS) score ≥ 6.0
• Individuals who have allergy or intolerance to soy isoflavones.
• Heart rate ≥110 or ≤40
• Any condition or therapy which, in the opinion of the investigator, might pose a risk to the participant or make participation in the study not in the participant's best interest
  • In addition, individuals with the following condition will be excluded because these conditions do not allow subjects to undergo examinations the investigators proposed in the project:
• Hearing impairment which interferes with cognitive testing
• Vision impairment which interferes with cognitive testing
• The investigators recruit subjects without dementia. Thus, at the initial screening by phone, the investigators exclude individuals whose score for the Telephone Interview for Cognitive Status is 22 and below. Then, at the screening visit, investigators will exclude individuals with a Quick Dementia Rating System score ≥ 6.0.

Lab values

• Hemoglobin \<10 g/dL
• HbA1c ≥ 7.5%
• Blood creatinine \> 2.0 mg/dL
• White blood cell count \<3,000 or \>15,000
• Platelet count \<100,000 or \>600,000
• \*1 Few studies have investigated the association of equol, a metabolite of soy isoflavone daidzein, with breast cancer. These studies reported no significant association of serum or urine equol with the risk of breast cancer. Dietary intake of soy and soy isoflavones is generally considered to have benefits for menopausal symptoms, cardiovascular health, bone health, and cancers of the breast and prostate. Observational studies show that soy consumption is associated with a reduced risk of many cancers including breast cancer. Moreover, a prospective cohort study of 6,000+ North American women with breast cancer showed that dietary intake of soy and isoflavones was associated with reduced all-cause mortality. However, there is little evidence to support that the use of supplements containing soy isoflavones or soy protein powder to reduce cancer risk. A recent large prospective cohort study in France reported that supplementation of soy isoflavones increased the risk of estrogen receptor-negative breast cancer, especially among women who had a history of breast cancer in first-degree relatives.

Other

• Individuals who are regularly taking isoflavone supplements or eat soy product ≥ 2 times a week (by specific questionnaire)
• Individuals who do not agree to maintain isoflavone supplements or soy product intake described above during the study period.
• Individuals whose score for the Telephone Interview for Cognitive Status is 22 and below.
• Individuals with untreated depression
• Individuals with atrial fibrillation
• Individuals with aortic (abdominal, thoracic) aneurysm
• Individuals currently undergoing hemodialysis
• Individuals unable to lay supine for 30-60 minutes
• Individuals with weight ≥300 lbs
• Individuals who are planning to move out of the area in the next 2 years
• Individuals who participated in another clinical trial in the past 3 months
• Individuals who are regularly taking isoflavone supplements or eat soy product ≥ 2 times a week (by specific questionnaire)
• Individuals who do not agree to maintain isoflavone supplements or soy product intake described above during the study period.
• Blood pressure (BP) - systolic BP ≥ 180 mmHg or diastolic BP ≥ 110 mmHg
• Liver function tests \> 2 X upper limit of normal
• Abnormal thyroid function (Thyroid Stimulating Hormone)
• Vitamin B12 levels ≤ 210 pg/mL
• Hematocrit \<30%
• Urinary protein ≥ + by dipstick
• Those who are contraindicated for 3 Tesla (3T) structural brain magnetic resonance imaging (MRI) such as pacemakers.
• Atrial fibrillation because pulse wave velocity is not accurately measured.

• Men and women age between 65 and 85 at entry of European Americans or African Americans
• Individuals who are able to provide informed consent
• Individuals who are willing to be randomized to the intervention or placebo group