Kyoko Taku

Extracted or synthesized soybean isoflavones reduce menopausal hot flash frequency and severity: systematic review and meta-analysis of randomized controlled trials

Objective This analysis was conducted to determine the efficacy of extracted or synthesized soybean isoflavones in the alleviation of hot flashes in perimenopausal and postmenopausal women. Methods PubMed and The Cochrane Controlled Clinical Trials Register Database were searched for relevant articles reporting double-blinded randomized controlled trials through December 14, 2010. References within identified articles, as well as peer-reviewed articles that had come to the attention of the authors through other means, were also examined for suitability. This systematic review and meta-analysis, which evaluated the effects of isoflavones on the frequency, severity, or composite score (frequency × severity) of hot flashes compared with placebo was conducted according to Cochrane Handbook guidelines. Results From 277 potentially relevant publications, 19 trials (reported in 20 articles) were included in the systematic review (13 included hot flash frequency; 10, severity; and 3, composite scores), and 17 trials were selected for meta-analyses to clarify the effect of soybean isoflavones on hot flash frequency (13 trials) and severity (9 trials). Meta-analysis revealed that ingestion of soy isoflavones (median, 54 mg; aglycone equivalents) for 6 weeks to 12 months significantly reduced the frequency (combined fixed-effect and random effects model) of hot flashes by 20.6% (95% CI, −28.38 to −12.86; P < 0.00001) compared with placebo (heterogeneity P = 0.0003, I 2 = 67%; random effects model). Meta-analysis also revealed that isoflavones significantly reduced hot flash severity by 26.2% (95% CI: −42.23 to −10.15, P = 0.001) compared with placebo (heterogeneity, P < 0.00001, I 2 = 86%; random effects model). Isoflavone supplements providing more than 18.8 mg of genistein (the median for all studies) were more than twice as potent at reducing hot flash frequency than lower genistein supplements. Conclusions Soy isoflavone supplements, derived by extraction or chemical synthesis, are significantly more effective than placebo in reducing the frequency and severity of hot flashes. Additional studies are needed to further address the complex array of factors that may affect efficacy, such as dose, isoflavone form, baseline hot flash frequency, and treatment duration.

Soy isoflavones for osteoporosis: An evidence-based approach

Effects of soy isoflavones on osteoporosis remain unclear. This review aimed to clarify the effect of soy isoflavones on bone mineral density (BMD) and turnover markers in menopausal women. PubMed and the Cochrane Library were searched in July 2011 for relevant meta-analyses of randomized controlled trials evaluating effects of soy isoflavones on BMD and bone turnover markers. Three meta-analyses evaluated the effects of soy isoflavones on lumbar spine, total hip, femoral neck, and trochanter BMD. Soy isoflavones significantly improved lumbar spine BMD in a moderate manner, but did not affect total hip, femoral neck, and trochanter BMD in menopausal women. Ingestion of soy isoflavones for six months appeared to be enough to exert a beneficial effect on lumbar spine BMD. Two meta-analyses evaluated the effects of soy isoflavones on a bone resorption marker (urine deoxypyridinoline) and two formation markers (serum alkaline phosphatase and osteocalcin). Soy isoflavones significantly decreased urine deoxypyridinoline in a moderate manner, but did not affect serum alkaline phosphatase and osteocalcin in menopausal women. Soy isoflavones may prevent postmenopausal osteoporosis and improve bone strength thus decreasing risk of fracture in menopausal women by increasing lumbar spine BMD and decreasing bone resorption marker urine deoxypyridinoline. Further studies are needed to address factors affecting the magnitude of the beneficial effects of soy isoflavones and to assess the possible interactions between soy isoflavones and anti-osteoporosis drugs, and to verify effects on BMD of other skeletal sites and other bone turnover markers.

Effects of soy isoflavone supplements on bone turnover markers in menopausal women: Systematic review and meta-analysis of randomized controlled trials

INTRODUCTION Effects of soy isoflavone supplements on bone turnover markers remain unclear. This up-to-date systematic review and meta-analysis of randomized controlled trials (RCTs) was performed primarily to more completely and precisely clarify the effects on urinary deoxypyridinoline (DPD) and serum bone alkaline phosphatase (BAP) and secondarily to evaluate the effects on other bone turnover markers, compared with placebo in menopausal women. METHODS PubMed, CENTRAL, ICHUSHI, and CNKI were searched in June 2009 for relevant studies of RCTs. Data on study design, participants, interventions, and outcomes were extracted and methodological quality of each included trial was assessed. RESULTS From 3740 identified relevant articles, 10 (887 participants), 10 (1210 participants), and 8 (380 participants) RCTs were selected for meta-analysis of effects on DPD, BAP, and serum osteocalcin (OC), respectively, using Review Manager 5.0.22. Daily ingestion of an average 56 mg soy isoflavones (aglycone equivalents) for 10 weeks to 12 months significantly decreased DPD by 14.1% (95% CI: -26.8% to -1.5%; P=0.03) compared to baseline (heterogeneity: P<0.00001; I(2)=93%; random effects model). The overall effect of soy isoflavones on DPD compared with placebo was a significant decrease of -18.0% (95% CI: -28.4% to -7.7%, P=0.0007; heterogeneity: P=0.0001; I(2)=73%; random effects model). Subgroup analyses and meta-regressions revealed that isoflavone dose and intervention duration did not significantly relate to the variable effects on DPD. Daily supplementation of about 84 mg and 73 mg of soy isoflavones for up to 12 months insignificantly increased BAP by 8.0% (95% CI: -4.2% to 20.2%, P=0.20; heterogeneity: P<0.00001; I(2)=98%) and OC by 10.3% (95% CI: -3.1% to 23.7%, P=0.13; heterogeneity: P=0.002; I(2)=69%) compared with placebo (random effects model), respectively. CONCLUSIONS Soy isoflavone supplements moderately decreased the bone resorption marker DPD, but did not affect bone formation markers BAP and OC in menopausal women. The effects varied between studies, and further studies are needed to address factors relating to the observed effects of soy isoflavones on DPD and to verify effects on other bone turnover markers.

Effects of soy isoflavone extract supplements on blood pressure in adult humans: systematic review and meta-analysis of randomized placebo-controlled trials.

Objective Reported effects of different soy products on blood pressure vary. This systematic review and meta-analysis was performed to clarify the effects of soy isoflavone extract supplements on systolic and diastolic blood pressure (SBP and DBP) in adult humans. Methods PubMed, CENTRAL, ICHUSHI, and CNKI were searched in June 2009 for relevant randomized placebo-controlled trials. Study data and indicators of methodological validity were independently extracted by two authors using predefined data fields. Meta-analysis was carried out in Review Manager 5.0.22. Results Searches identified 3740 articles, of which 14 randomized controlled trials (789 participants) were included. Daily ingestion of 25–375 mg soy isoflavones (aglycone equivalents) for 2–24 weeks significantly decreased SBP by 1.92 mmHg (95% confidence interval −3.45 to −0.39; P = 0.01) compared with placebo (heterogeneity P = 0.39, fixed effect model) in adults with normal blood pressure and prehypertension. The effect was not lost on sensitivity analysis. Subgroup analyses suggest greater effects in studies longer than 3 months, in Western populations, at lower doses, and in studies at lower risk of bias. Soy isoflavones did not affect DBP [−0.13 (95% confidence interval −1.03 to 0.78) mmHg, P = 0.78; heterogeneity P = 0.20, fixed effect model]. Conclusion Soy isoflavone extracts significantly decreased SBP but not DBP in adult humans, and no dose–response relationship was observed. Further studies are needed to address factors related to the observed effects of soy isoflavones on SBP and to verify the effect in hypertensive patients.

Effects of extracted soy isoflavones alone on blood total and LDL cholesterol: Meta-analysis of randomized controlled trials

When provided concurrently with soy protein for 1–3 months, soy isoflavones exert synergistic or additive cholesterol-lowering effects. This meta-analysis was performed to evaluate the effects of extracted soy isoflavones alone (not ingested concurrently with soy protein) on total and low density lipoprotein (LDL) cholesterol. MEDLINE (1966–2007), EMBASE (1966–2007), CENTRAL (1966–2007), ICHUSHI (1983–2008), and CNKI (1979–2007) were searched for randomized placebo-controlled trials published in English, Japanese, and Chinese, describing the changes in lipid profiles in adult humans resulting from ingestion of extracted soy isoflavones for 1–3 months. Reference lists of relevant systematic reviews and meta-analyses were hand-searched. Meta-analysis of 10 and 9 trials with usable information using REVMAN found that an average of 70 mg soy isoflavones/day (27–132 mg, as the aglycone form) alone had a nonsignificant effect on total (0.01 mmol/L [95% CI: –0.12, 0.14]; P = 0.86) and LDL (0.03 mmol/L [95% CI: –0.11, 0.16]; P = 0.71) cholesterol in menopausal women, respectively. It is concluded that ingestion of about 70 mg extracted soy isoflavones/day alone for 1–3 months does not improve total and LDL cholesterol levels in normocholesterolemic menopausal women; further studies are needed to verify the effects of extracted soy isoflavones.

Bilobalide in Ginkgo biloba extract is a major substance inducing hepatic CYPs.

In a search for substances related to the marked induction of hepatic cytochrome P450 (CYP) by ginkgo biloba extract (GBE), mice were given either GBE (1000 mg kg−1) or fractions of GBE for 5 days. The content and activity of CYPs were induced markedly by a bilobalide‐rich fraction, but not by flavonoid‐rich fractions. The level of induction by the bilobalide‐rich fraction was almost the same as that induced by the unfractionated GBE, suggesting that bilobalide is largely responsible for the CYPs induction. To confirm these findings, mice were given various doses of bilobalide (10.5, 21 and 42 mg kg−1), or GBE (1000 mg kg−1, containing bilobalide at 42 mg kg−1). Treatment with bilobalide induced CYPs markedly and in a dose‐dependent manner, and the level of induction was quite similar between bilobalide (42 mg kg−1) and GBE. Treatment with GBE and with bilobalide greatly induced pentoxyresorufin O‐dealkylase activity. These findings indicate that bilobalide is the major substance in GBE that induces hepatic CYPs.

Estimated Average Daily Intake of Antioxidants from Typical Vegetables Consumed in Japan : A Preliminary Study

The hydrophilic antioxidant content of 23 vegetables commonly consumed in Japan was assessed by the hydrophilic oxygen radical absorbance capacity (H-ORAC) method to estimate the dietary intake of total antioxidants in Japan. The estimated average H-ORAC value for “typical vegetables” consumed in Japan was 594.3 μmol Trolox equivalent (TE)/100 g. Hence, 2080 μmol TE/d of hydrophilic antioxidants would be ingested when 350 g of vegetables a day are consumed.

Serum lipid-improving effect of soyabean β-conglycinin in hyperlipidaemic menopausal women.

To evaluate the effect of treatment with β-conglycinin, a major soyabean protein, on blood lipids in menopausal women, we recruited 100 hyperlipidaemic women aged 40-60 years old. Participants were randomly allocated to three groups: placebo group (n 34, four casein tablets/d); low dose group (n 33, four tablets containing 2·3 g β-conglycinin/d); high-dose group (n 33, eight tablets containing 4·6 g β-conglycinin/d). The mean serum TAG concentration was significantly reduced after 6 and 12 weeks of β-conglycinin intervention by 0·44 (sd 0·20) and 0·78 (sd 1·03) mmol/l in the low-dose group, and by 0·46 (sd 0·17) and 1·25 (sd 1·06) mmol/l in the high-dose group, respectively. One-way ANOVA revealed that serum TAG concentrations in the low-dose and high-dose groups were significantly lowered compared with the placebo group at weeks 6 and 12 (P< 0·05). The low dose and high dose consumptions of β-conglycinin significantly decreased the LDL-cholesterol concentration by 0·46 (sd 0·72) and 0·52 (sd 0·97) mmol/l at week 12, respectively (P< 0·05). Compared with the changes from baseline in the placebo group, apoB and NEFA were significantly lowered in both the low-dose and high-dose β-conglycinin groups (P< 0·05). In conclusion, the results suggest that β-conglycinin intake significantly decreases serum TAG and LDL-cholesterol levels.