Short-term effects and safety of a natural oral supplement containing glucosinolates, phytosterols, and citrus flavonoids compared with hormone treatment for the management of postmenopausal symptomatic women: a pilot single-center randomized phase 2 clinical trial.

OBJECTIVE: This study aimed to evaluate the short-term efficacy and safety of an oral herbal supplement containing glucosinolates, phytosterols, and citrus flavonoids for menopausal symptoms in comparison with estrogen plus progestogen therapy (EPT) among postmenopausal women. METHODS: This was a pilot single-blinded, three-armed phase II randomized clinical trial, controlled with EPT. Sixty participants were randomly assigned to receive treatment for 3 months: (1) an oral herbal supplement of 1,500 mg/d (G1, n = 20), (2) an oral herbal supplement of 3,000 mg/d (G2, n = 20), or (3) conjugated equine estrogens 0.625 mg/d plus medroxyprogesterone acetate of 5 mg/d (EPT group, n = 20). The primary endpoint was the intensity of menopausal symptoms as measured using the Menopause-Specific Quality of Life Questionnaire (global and domain scores). The Menopause-Specific Quality of Life Questionnaire uses a 7-point scale to rate the symptom intensity, with higher scores indicating severity. The secondary endpoints were hormonal, lipid, and safety profiles. RESULTS: Fifty-four participants (n = 54) completed the study. The mean, model-estimated, and global menopausal symptom scores at 3 months were 85.8 in the EPT group, 61.3 in G1, and 62.5 in G2. Participants treated with the herbal compound had lower global (13.7 [6.9-20.4], P < 0.001) and physical symptom scores (6.6 [1.6-11.5], P = 0.002) on the second month and lower psychosocial symptom scores (3.8 [1.3 to 6.3], P < 0.001) on the third month of follow-up, compared with EPT. Conversely, participants receiving EPT showed better outcomes on vasomotor symptoms since the first month of treatment (-6.1 [-8.3 to -4.0], P < 0.001). The EPT group exhibited higher values of estradiol and lower follicle-stimulating hormone and luteinizing hormone since the first month of follow-up. Also, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were significantly higher in this group than in G2. CONCLUSIONS: In this small single-blind exploratory trial, the oral herbal supplement was more efficacious in reducing global, physical, and psychosocial menopausal symptoms in the short term than EPT. However, further studies are needed to adequately assess the efficacy and safety of this herbal supplement in the treatment of menopausal symptoms.

Safety and tolerability of a natural supplement containing glucosinolates, phytosterols and citrus flavonoids in adult women: a randomized phase I, placebo-controlled, multi-arm, double-blinded clinical trial.

OBJECTIVE: To evaluate the safety and tolerability of an oral herbal supplement containing glucosinolates, phytosterols, and citrus flavonoids (Warmi®, Lima Perú;) in otherwise healthy adult women. METHODS: This was a phase-I, randomized parallel three arms, double-blinded, and a placebo-controlled clinical trial. A total of 55 participants aged 18-40 were randomly assigned to one of three groups to receive for three months: (1) an oral herbal supplement of 1650 mg/day; (2) an oral herbal supplement of 3300 mg/day; or (3) an oral placebo 3300 mg/day. The primary endpoints were oral safety and tolerability of the supplement. The secondary endpoint was its effect on vital functions, anthropometrics, and laboratory tests. We used an exploratory approach by covariance analysis (ANCOVA) adjusted for the variables' baseline value for the secondary outcomes. RESULTS: All women completed three months of follow-up, reporting no side effects. Our exploratory analysis revealed that treatment with the herbal supplement of 1650 mg/day was associated with increased glucose and uric acid levels. In comparison, the herbal supplement 3300 mg/day was associated with reduced breathing rate, increased basal temperature, and systolic blood pressure, both compared to the placebo group. However, despite significant differences, none of these was clinically significant. CONCLUSION: The oral herbal supplement had a favorable safety and tolerability profile in studied women. There is a need to study its potential as an option to treat menopausal symptoms.

Effect of a natural supplement containing glucosinolates, phytosterols and citrus flavonoids on body weight and metabolic parameters in a menopausal murine model induced by bilateral ovariectomy.

OBJECTIVE: To evaluate the effect of a herbal preparation containing glucosinolates, phytosterols and citrus flavonoids (supplement) on body weight and metabolic parameters usually impaired by menopause. METHODS: A pre-clinical experimental study carried out in twenty-five Swiss strain mice (Mus musculus) randomly distributed (1:1:1:1:1 ratio) to five groups to receive for ten weeks: (1) oral gelatinized maca extract 0.5625 mg/kg/day + bilateral ovariectomy (Maca + OVX); (2) oral supplement 0.5625 mg/kg/day + bilateral ovariectomy (S1 + OVX); (3) oral supplement 1.6875 mg/kg/day + bilateral ovariectomy (S2 + OVX); (4) oral saline 100 µl/kg/day + bilateral ovariectomy (OVX); and (5) oral saline 100 µl/kg/day + sham surgery (sham). The primary endpoint was change in body weight gain from baseline to final. Secondary endpoints were uterine weight and cholesterol, triglyceride, glucose, and glucose/triglycerides index values at the end of the study. A modified intention-to-treat analysis was performed through linear regression models and using the Bonferroni method to penalized p-values by multiple comparisons. RESULTS: Twenty-three animals completed the study. There was a significant average difference in weight gain, with a greater reduction in the S2 + OVX group compared to the OVX group (difference= -3.5; 95% CI (-5.27; -1.74); p < .001). S2 + OVX group also displayed a significant average reduction of total blood cholesterol (difference: -16.94; 95% CI (-33.73; -0.15); p = .037). No significant effects of the supplement were found on other secondary endpoints. CONCLUSION: In this murine menopausal model, triple oral supplement dose resulted in an average reduction of weight gain and total cholesterol levels, suggesting that the compound could have a potential effect at regulating menopausal altered metabolism.

Effect of vitamin D supplementation during pregnancy on maternal and neonatal outcomes: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To assess the effects of vitamin D supplementation during pregnancy on obstetric outcomes and birth variables. DESIGN: Systematic review and meta-analysis of randomized controlled trials (RCTs). SETTING: Not applicable. PATIENT(S): Pregnant women and neonates. INTERVENTION(S): PubMed and 5 other research databases were searched through March 2014 for RCTs evaluating vitamin D supplementation ± calcium/vitamins/ferrous sulfate vs. a control (placebo or active) during pregnancy. MAIN OUTCOME MEASURE(S): Measures were: circulating 25-hydroxyvitamin D [25(OH)D] levels, preeclampsia, gestational diabetes mellitus (GDM), small for gestational age (SGA), low birth weight, preterm birth, birth weight, birth length, cesarean section. Mantel-Haenszel fixed-effects models were used, owing to expected scarcity of outcomes. Effects were reported as relative risks and their 95% confidence intervals (CIs). RESULT(S): Thirteen RCTs (n = 2,299) were selected. Circulating 25(OH)D levels were significantly higher at term, compared with the control group (mean difference: 66.5 nmol/L, 95% CI 66.2-66.7). Birth weight and birth length were significantly greater for neonates in the vitamin D group; mean difference: 107.6 g (95% CI 59.9-155.3 g) and 0.3 cm (95% CI 0.10-0.41 cm), respectively. Incidence of preeclampsia, GDM, SGA, low birth weight, preterm birth, and cesarean section were not influenced by vitamin D supplementation. Across RCTs, the doses and types of vitamin D supplements, gestational age at first administration, and outcomes were heterogeneous. CONCLUSION(S): Vitamin D supplementation during pregnancy was associated with increased circulating 25(OH)D levels, birth weight, and birth length, and was not associated with other maternal and neonatal outcomes. Larger, better-designed RCTs evaluating clinically relevant outcomes are necessary to reach a definitive conclusion.

Soy extracts versus hormone therapy for reduction of menopausal hot flushes: indirect comparison.

OBJECTIVE: The aim of this study was to make an indirect comparison of the results from meta-analyses that evaluated the severity of hot flushes in postmenopausal women exposed to hormone therapy (HT) or soy extracts. METHODS: A systematic review and meta-analysis of HT and soy extracts related to the reduction of hot flushes in postmenopausal women versus the same control (placebo) were conducted. In addition, the combination of the overall results obtained from these two meta-analyses (indirect comparison) was adjusted to the common control (placebo). RESULTS: The indirect standardized mean difference (SMD) obtained from the combination of both individual meta-analyses was calculated by using the following equation: SMD(indirect SOY vs HT) = SMD(soy) - SMD(HT), with a total indirect variance (var) equivalent to the following equation: var(total) = var(soy) + var(HT). These calculations yielded a point estimate of -0.84 (95% CI, -1.33 to -0.35) for the indirect SMD favorable to HT. CONCLUSIONS: HT and soy interventions showed a significant difference in efficacy for the reduction of hot flushes in postmenopausal women when each treatment was compared with placebo. However, using indirect comparison, there is a statistically significant difference between HT and soy extracts in their effects on hot flushes.