Equol Supplementation Improves Bone and Cardiovascular Health in Middle-aged Women

Equol is a metabolite produced by the action of intestinal bacteria on the soy (Glycine max, Fabaceae) isoflavone daidzein. It has some effects similar to those of the hormone estrogen. Some evidence suggests that the efficacy of soy depends on an individual’s ability to produce equol. The authors, from medical centers in Minato-ku, Japan, conducted a prospective, observational study to examine changes in bone and cardiovascular parameters among women taking equol for one year, to identify the factors affecting the changes, and to assess any adverse effects associated with the use of equol.

The study began with 105 postmenopausal females who visited the Hamasite Medical Clinic from 2013 to 2015 for medical complaints that might be favorably affected by equol. Of those 105 women, 74 females aged 44 to 74 years completed the 12-month study with blood and urine testing for bone and cardiovascular parameters. The 74 patients took 20 mg equol daily for 12 months. Twenty-two of those patients were also treated with hormone replacement therapy (HRT) by transversal patch every two weeks based on troubling menopausal symptoms and medical history.

Equol was administered in FlavoCel EQ-5 (Daicel Corporation; Tokyo, Japan) capsules, containing 98% S-equol, 2% daidzein, 0.2% glycitein, and 0.1% genistein extracted from fermented soybeans. The transdermal HRT patch Menoaid Combipatch (Aska Pharmaceutical Co., Ltd.; Tokyo, Japan) contained 0.62 mg estradiol and 2.7 mg norethisterone acetate.

Baseline urine samples were collected to measure levels of equol, calcium, and N-telopeptide (NTX, a marker of bone resorption). Patients with a urinary equol level higher than 1.0 µmol/L were considered to be equol producers. Blood samples were drawn to measure lipid levels, intact parathyroid hormone (PTH), calcium, phosphorous, and procollagen type 1 propeptide. Arterial stiffness was measured by using brachial-ankle pulse wave velocity (baPWV). Clinical signs and symptoms were monitored monthly; liver and kidney function tests and complete blood counts were done after six and 12 months. Pap smear, transvaginal ultrasound, and mammography were done at baseline and at the end of the study.

The baseline baPWV was lower, though not significantly, in the 25 equol producers compared with the 47 nonproducers. No significant differences in lipid and bone parameters were observed between producers and nonproducers at baseline.

At three months, significant reductions in baPWV were seen in the equol group. In the 74 patients who completed the study, significant reductions were seen in arterial stiffness (P<0.01), and increases were seen in total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) (P<0.01 for all). The LDL/HDL ratios did not change. “These results were hard to discern and further well-designed clinical trials are warranted to examine the effects of equol on blood cholesterol level,” wrote the authors.

Significant reductions in baPWV were seen in patients with moderate to high risk for arteriosclerosis compared with those at normal risk (P=0.007). Patients with hypertriglyceridemia experienced greater reductions in triglyceride levels compared with those with normal triglyceride levels (P=0.004). Greater reductions in NTX were seen in patients at high risk for bone resorption and bone fracture at baseline compared with those at normal risk (P=0.002).

A 50% reduction in PTH values was seen in 15 patients with high baseline PTH values. The authors suggest that equol’s estrogenic action might be responsible for reducing PTH levels. Climacteric symptoms were significantly improved regardless of equol-producing ability. No adverse effects or abnormal findings in safety measures were reported.

The limitations of this study include the lack of consideration of changes in diet or supplement use, which may have affected the outcomes; the lack of a placebo group; and the small sample size.

In this study, equol supplementation for one year was tolerable and improved certain bone and cardiovascular parameters in middle-aged women. The authors declared no conflict of interest.


Yoshikata R, Myint KZY, Ohta H. Effects of equol supplement on bone and cardiovascular parameters in middle-aged Japanese women: a prospective observational study. J Altern Complement Med. July 2018;24(7):701-708. doi: 10.1089/acm.2018.0050.