Effect of whole soy and isoflavones daidzein on bone turnover and inflammatory markers: a 6-month double-blind, randomized controlled trial in Chinese postmenopausal women who are equol producers

Abstract

Background: Human studies have demonstrated the beneficial effects of soy or isoflavones on bone metabolism. However, conflicting data remain. Equol is the intestinal metabolite of the isoflavone daidzein. The health benefits of soy are more pronounced in equol producers than those not producing equol. This 6-month randomized controlled trial aimed to examine the effect of whole soy (soy flour) and purified daidzein on bone turnover markers (BTMs) in Chinese postmenopausal women who are equol producers. Methods: A total of 270 eligible women were randomized to either one of the three isocaloric supplements as follows: 40 g soy flour (whole soy group), 40 g low-fat milk powder + 63 mg daidzein (daidzein group), or 40 g low-fat milk powder (placebo group) given as a solid beverage daily for 6 months. The following fasting venous samples were collected at the baseline and end of the trial to analyze BTMs: serum cross-linked C-telopeptides of type I collagen, bone-specific alkaline phosphatase, osteocalcin, procollagen type I N-terminal propeptide, and 25(OH)D3. Inflammation-related biomarkers, such as serum interleukin-6, tumor necrosis factor-alpha, C-reactive protein, transferrin, and homocysteine, were also tested to explore potential mechanisms. Results: A total of 253 subjects validly completed the study protocol. Urinary isoflavones suggested a good compliance to the treatments. Intention-to-treat and per-protocol analyses indicated no significant difference in the 6-month or percentage changes in the parameters of bone metabolism and inflammatory markers among the three treatment groups. Conclusions: Whole soy and purified daidzein at provided dosages exhibited no significant effect on the bone metabolism and inflammation levels among Chinese equol-producing postmenopausal women. Trial registration: ClinicalTrials.gov identifier NCT01270737.

Main drivers of (poly)phenol effects on human health: metabolite production and/or gut microbiota-associated metabotypes?

“…Two randomised placebo-controlled trials (RCT) specifically recruited equol-producing participants to evaluate isoflavone effects on blood pressure, vascular function, 155 bone metabolism and inflammation. 156 Remarkably, the authors did not observe a significant effect on any cardiovascular risk factor among 253 Chinese equol-producing postmenopausal women that consumed isoflavones for 6 months. 156 Unfortunately, whether the same approach could have exerted some effects on equol non-producers remains unanswered.…”

“…156 Remarkably, the authors did not observe a significant effect on any cardiovascular risk factor among 253 Chinese equol-producing postmenopausal women that consumed isoflavones for 6 months. 156 Unfortunately, whether the same approach could have exerted some effects on equol non-producers remains unanswered. Recently, an 8.8-years prospective study described that serum isoflavones and equol were associated with reduced carotid intima-media thickness progression, mediated by sex hormone-binding globulins and systolic blood pressure in 2,572 Chinese subjects (40-75 years old).…”

Anti-Inflammation Activity of Flavones and Their Structure–Activity Relationship

“…In another double-blind clinical trial, intake of 50–150 mg of quercetin daily with 35 healthy volunteers for 2 weeks did not improve the antioxidant status, oxidized low-density lipoprotein (LDL), inflammation, or metabolism, although quercetin concentration increased in plasma . Regarding isoflavone, a 6-month randomized controlled trial recruiting 270 equol-producing postmenopausal women revealed that the daily consumption of 63 mg of daidzein (precursor of equol) led to no significant effects on inflammatory markers . It is worth mentioning that some ongoing clinical trials are examining the anti-inflammatory effect and adjuvant benefits of flavones (e.g., quercetin, hesperidin, and baicalein) on coronavirus disease 2019 (COVID-19), and we expect some good outcomes.…”

“…101 Regarding isoflavone, a 6-month randomized controlled trial recruiting 270 equol-producing postmenopausal women revealed that the daily consumption of 63 mg of daidzein (precursor of equol) led to no significant effects on inflammatory markers. 102 It is worth mentioning that some ongoing clinical trials are examining the anti-inflammatory effect and adjuvant benefits of flavones (e.g., quercetin, hesperidin, and baicalein) on coronavirus disease 2019 (COVID-19), and we expect some good outcomes. Taken together, although many flavones are reported as antiinflammatory agents in vitro, in vivo, and in clinical studies, more high-quality clinical studies are needed to establish strong evidence on the effects of individual flavone aglycones on the prevention and treatment of inflammation.…”

Vasomotor Symptoms

“…Interventions include nonhormonal medications, botanicals and supplements, acupuncture, and lifestyle changes. Demonstrating the superiority of these interventions over placebo is challenging because of the robust placebo effect (20-60%), strongest in women with associated anxiety and stronger baseline symptoms, found in all studies of VMS treatments [30][31][32].…”