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

• Status: Not yet recruiting
• Trial end date: 2026-04-01
• Target enrollment: 0
• Participant gender: All

Summary

The ACE Trial, funded by the National Institute on Ageing/National Institutes of Health (NIH), is a multicenter clinical trial. The ACE Trial will determine if taking the dietary supplement Equol could slow the progression of stiffening of the arteries, small blood vessel disease in the brain and memory decline. Equol is a soy-based supplement that has plant estrogen-like compounds in it.

Equol is a metabolite of soy isoflavone. Our studies in Japan and other studies suggest that Equol may slow mechanisms related to memory decline. No previous studies in the United States have tested the effect of Equol on these mechanisms or memory decline. Supplementation of Equol in the ACE Trial is approved by the Food and Drug Administration (FDA).

Researchers at the University of Pittsburgh, Pittsburgh, Pennsylvania, Wake Forest University, Winston-Salem, North Carolina, and Emory University, Atlanta, Georgia, are recruiting participants.

The ACE Trial will ask participants to complete 7 clinic visits over a two-year period. The participants are asked to take Equol tablets daily for 24 months. Clinic procedures include Pulse Wave Velocity (to measure arterial stiffness), Magnetic Resonance Imaging (MRI) of the brain and tests of awareness and thinking.

• Phase: Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Akira Sekikawa
• Collaborator: National Institute on Aging (NIA)
• Treatments: Equol

Criteria

Inclusion Criteria:

Men and women age between 65 and 85 at entry of European Americans or African Americans

Inclusion criteria via screening visit:

• Individuals who are able to provide informed consent

• Individuals who are willing to be randomized to the intervention or placebo group

Exclusion Criteria:

Exclusion criteria via initial screening by phone

• 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 who have allergy or intolerance to soy isoflavones.

• Individuals whose score for the Telephone Interview for Cognitive Status is 22 and below.

• Individuals with stroke, neurological disorders, major depression/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 untreated depression

• Individuals with atrial fibrillation

• Individuals with heart failure

• Individuals with heart attack or coronary intervention in the past 6 months

• Individuals with carotid endartectomy or peripheral artery disease

• Individuals currently undergoing treatment for pulmonary embolism or deep vein thrombosis

• Individuals with inflammatory bowel diseases

• Individuals currently undergoing hemodialysis

• Women with a past or family history of breast cancer.*1

• Women on estrogen replacement therapy

• Individuals unable to lay supine for 30-60 minutes

• Individuals with BMI ≥40

• 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

Exclusion criteria via screening visit

• Individuals with QDRS score ≥ 6.0

• 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 who have allergy or intolerance to soy isoflavones.

• Blood pressure (BP) - systolic BP ≥ 180 mmHg or diastolic BP ≥ 110 mmHg

• Heart rate ≥110 or ≤40

• Hemoglobin <10 g/dL

• HbA1c ≥ 7.5%

• Blood creatinine > 2.0 mg/dL

• Liver function tests > 2 X upper limit of normal

• Abnormal thyroid function (Thyroid Stimulating Hormone)

• Vitamin B12 levels ≤ 210 pg/mL

• Hematocrit <30%

• White blood cell count <3,000 or >15,000

• Platelet count <100,000 or >600,000

• Urinary protein ≥ + by dipstick

• 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 we proposed in the project:

• Those who are contraindicated for 3T structural brain magnetic resonance imaging (MRI) such as pacemakers.

• Atrial fibrillation because pulse wave velocity is not accurately measured.

• Hearing impairment which interferes with cognitive testing

• Vision impairment which interferes with cognitive testing

Exclusion criteria at structural brain MRI Any other conditions 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

*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.

Exclusion criteria at the baseline visit

We recruit subjects without dementia. Thus, at our initial screening by phone, we exclude individuals whose score for the Telephone Interview for Cognitive Status is 22 and below. Then, at our screening visit, we will exclude individuals with a Quick Dementia Rating System score ≥ 6.0.