Stachys schtschegleevii tea, matrix metalloproteinase, and disease severity in female rheumatoid arthritis patients: a randomized controlled clinical trial.

BACKGROUND: Stachys schtschegleevii (SSC) is a herbal medicine used to treat infections. To date, this is the first study aimed to investigate the effects of SSC tea on disease activity score (DAS), serum inflammatory biomarkers and matrix metalloproteinases (MMP-1 and MMP-3) among women with rheumatoid arthritis (RA). METHODS: This pilot, triple-blind, randomized controlled clinical trial was conducted among forty-four women (age: 30-65 years) diagnosed with moderately active RA. Subjects were randomly assigned (1:1 ratio) into either SSC group (2.4 g/day SSC + 2.4 g/day black tea, n=22) or placebo (2.4 g/day black tea, n=22) for 8 weeks. Serum high-sensitivity C-reactive protein (hs-CRP), interleukin-1 beta (IL-1ß), and MMPs were measured using ELISA. According to the American College of Rheumatology guideline considering hs-CRP, DAS28 was assessed. RESULTS: Both study groups had respondent rates above 94.9%. The SSC intervention caused significant reductions in the number and the percent changes of the tender joints (SSC: -74.39% vs. placebo: -57.15%, mean differences= -0.77; P<0.05) and DAS28 [SSC: -32.44% vs. placebo: -22.32%, mean differences= -0.41, P<0.05). Unlike the intervention within SSC group that showed significant reductions in the mean serum levels of hs-CRP, IL-1ß, and MMP-3, SSC caused significant MMP-3 reductions (SSC: -20.59% vs. placebo: 1.29%, P<0.05). CONCLUSION: The SSC intervention showed an appropriate clinical efficacy for female RA patients, accompanying remarkable reductions in the number of tender and swollen joints, DAS28, and serum levels of MMP-3. This can provide additional insights to the interventional studies controlling RA-related pathological and inflammatory outcomes. Trial registration Prospectively registered at the Iranian Registry of Clinical Trials (IRCT), linked to the WHO Registry Network ( https://en.irct.ir/trial/11602 , IRCT registration number: IRCT2015032011335N5, Registration date:2015-05-12). Key Points • Stachys schtschegleevii improved clinical outcomes and attenuated disease severity in RA patients. • Stachys schtschegleevii ameliorated serum level of MMP-3 in RA patients.

Effects of cholecalciferol supplementation on serum angiogenic biomarkers in breast cancer patients treated with tamoxifen: A controlled randomized clinical trial.

OBJECTIVE: The aim of this study was to investigate the effects of cholecalciferol supplementation on serum levels of angiogenic parameters in patients with breast cancer (BC) who were treated with tamoxifen. METHODS: This was a pilot-based, randomized, triple-blind, placebo-controlled clinical trial with 52 patients with BC randomly assigned to either an intervention group receiving weekly 50 000 IU cholecalciferol or a placebo group for 8 wk. At baseline and at end of study, serum levels of angiogenic growth factors such as vascular endothelial growth factor (VEGF)-A, angiopoietin (Ang)-2, hypoxia-inducible factor (Hif)-1, and high-sensitivity C-reactive protein were measured by enzyme-linked immunosorbent assay. Every 4 wk, a completed 3-d, 24-h dietary record and daily sunlight exposure checklist were collected and anthropometric variables were measured. RESULTS: The ultimate number of participants in each arm was 22 for analyses. For premenopausal women, cholecalciferol supplementation resulted in a significant decrease in serum levels of Ang-2 and VEGF-A after 8 wk of treatment (P < 0.05). In the absence of vascular invasion, supplementation led to a significant decrease in Ang-2 levels compared with the placebo group (P < 0.05). Supplementation caused significant increases in Hif-1 in patients diagnosed with the infiltration of tumors into vascular or lymphatic vessels (P < 0.05). CONCLUSION: Cholecalciferol supplementation achieved sufficient efficacy among patients with BC taking tamoxifen and could be effective in the reduction of angiogenic biomarkers particularly dependent on the infiltration status of the tumor to vessels. Further studies with larger subgroups should be investigated.

The effects of Berberis vulgaris consumption on plasma levels of IGF-1, IGFBPs, PPAR-γ and the expression of angiogenic genes in women with benign breast disease: a randomized controlled clinical trial.

BACKGROUND: The present study was designed to investigate the effects of Berberis vulgaris (BV) juice consumption on plasma levels of insulin-like growth factor (IGF-1), IGF-binding proteins (IGFBPs), and the expression of PPAR-γ, VEGF and HIF in women with benign breast disease. METHODS: This parallel design randomized, double-blind controlled clinical trial was conducted on 85 eligible patients diagnosed with benign breast disease. They were assigned randomly into either BV juice group (n = 44, BV juice: 480 ml/day) or placebo group (n = 41, BV placebo juice: 480 ml/day) for 8 weeks intervention. Participants, caregivers and those who assessed laboratory analyses were blinded to the assignments. Plasma levels of biomarkers were measured at baseline and after 8 weeks by ELISA. Quantitative real-time PCR was used to measure the fold change in the expression of each interested gene. RESULTS: The compliance of participants was 95.2% and 40 available subjects analyzed in each group at last. Relative treatment (RT) effects for BV juice caused 16% fall in IGF-1 concentration and 37% reduction in the ratio of IGF-1/1GFBP1. Absolute treatment effect expressed 111 ng/ml increased mean differences of IGFBP-3 between BV group and placebo. Plasma level of PPAR-γ increased in both groups but it was not significant. Fold changes in the expressions of PPAR-γ, VEGF and HIF showed down-regulation in the intervention group compared to placebos (P < 0.05). CONCLUSIONS: The BV juice intervention over 8 weeks was accompanied by acceptable efficacy and decreased plasma IGF-1, and IGF-1/IGFBP-1 ratio partly could be assigned to enhanced IGFBP-1 level in women with BBD. The intervention caused reductions in the expression levels of PPAR, VEGF, and HIF which are remarkable genomic changes to potentially prevent breast tumorigenesis. TRIAL REGISTRATION: IRCT2012110511335N2. Registered 10 July 2013 (retrospectively registered).

The contribution of dietary and plasma folate and cobalamin to levels of angiopoietin-1, angiopoietin-2 and Tie-2 receptors depend on vascular endothelial growth factor status of primary breast cancer patients.

The aim of this study was to determine the association of dietary folate and cobalamin with plasma levels of Angiopoietins (ANG), vascular endothelial growth factor-C (VEGF-C) and tyrosine kinase receptor-2 (Tie-2) of primary breast cancer patients. Women (n = 177), aged 30 to 75 years diagnosed with breast cancer were recruited from an ongoing case series study. Dietary intake of nutrients was estimated by using a validated food frequency questionnaire. Enzyme-linked immunosorbent assay was applied to measure biomarkers. MCF-7 cell cultures were supplemented with folic acid (0-40 µM) for 24 h to measure cell viability and fold change of expression by the real-time reverse transcriptase-polymerase chain reaction. Structural equation modeling was applied to analyze the structural relationships between the measured variables of nutrients and Angiopoietins. Dietary intake of folate and cobalamin showed a significant inverse correlation with plasma ANG-1 and ANG-2 (P < 0.05), particularly in subjects with estrogen-receptor positive tumors or low plasma VEGF-C. Plasma folate was positively associated with the ratio of ANG-1/ANG-2 (P < 0.05). Residual intake levels of total cobalamin were inversely associated with plasma ANG-1 when plasma stratum of VEGF-C was high (P < 0.05). Structural equation modeling identified a significant inverse contribution of folate profiles on the latent variable of Angiopoietins (coefficient ß = -0.99, P < 0.05). Folic acid treatment resulted in dose-dependent down-regulations on ANGPT1 and ANGPT1/ANGPT2 ratio but VEGF and ANGPT2/VEGF were upregulated at folic acid >20 µM. Studying the contributing role of dietary folate to pro-angiogenic biomarkers in breast cancer patients can infer the preventive role of folate in the ANGs/VEGF-C-dependent cascade of tumor metastasis. By contrast, high concentrations of folic acid in vitro supported VEGF-C-dependent ANGPT2 overexpression might potentiate micro-lymphatic vessel development to support malignant cell dissemination.

Consumption of Fresh Yellow Onion Ameliorates Hyperglycemia and Insulin Resistance in Breast Cancer Patients During Doxorubicin-Based Chemotherapy: A Randomized Controlled Clinical Trial.

PURPOSE: Doxorubicin has been found to be associated with insulin resistance in animal models. Onion, a so-called functional food, is noted to affect the insulin signaling pathway of diabetes in vitro. To our knowledge, this is the first study to investigate the effects of consuming fresh yellow onions on insulin-related indices compared with a low-onion-containing diet among breast cancer (BC) patients treated with doxorubicin. METHODS: This parallel-design, randomized, triple-blind, controlled clinical trial was conducted on 56 eligible BC patients (aged 30-63 years), diagnosed with invasive ductal carcinoma. Following their second cycle of chemotherapy, subjects were assigned in a stratified-random allocation to receive body mass index-dependent 100 to 160 g/d of onion as high onion group (HO; n = 28) or 30 to 40 g/d small onions in low onion group (LO; n = 28) for 8 weeks intervention. Participants, care givers, and those who assessed laboratory analyses were blinded to the assignments (IRCT Registry No.: IRCT2012103111335N1). RESULTS: The compliance level of participants in the analysis was as high as 87.85%. A total of 23 available cases was analyzed in each group. The daily use of HO resulted in a significant decrease in serum fasting blood glucose and insulin levels in comparison with LO, over the period of study ( P < .001). Posttreatment with HO showed a significant decrease in homeostasis model of assessment-insulin resistance relative to changes in the LO group ( P < .05). A comparison of the changes that occurred throughout pre- and postdose treatments indicated improved quantitative insulin sensitivity check index ( P < .05) and controls on C-peptide in the HO group ( P < .05). CONCLUSIONS: The present study demonstrated the effectiveness of onion to ameliorate hyperglycemia and insulin resistance in BC during doxorubicin-based chemotherapy.

Effects of Fresh Yellow Onion Consumption on CEA, CA125 and Hepatic Enzymes in Breast Cancer Patients: A Double- Blind Randomized Controlled Clinical Trial.

Onion (Allium cepa) consumption has been remarked in folk medicine which has not been noted to be administered so far as an adjunct to conventional doxorubicin-based chemotherapy in breast cancer patients. To our knowledge, this is the first study aimed to investigate the effects of consuming fresh yellow onions on hepatic enzymes and cancer specific antigens compared with a low-onion containing diet among breast cancer (BC) participants treated with doxorubicin. This parallel design randomized controlled clinical trial was conducted on 56 BC patients whose malignancy was confirmed with histopathological examination. Subjects were assigned in a stratified-random allocation into either group received body mass index dependent 100-160 g/d of onion as high onion group (HO; n=28) or 30-40 g/d small onion in low onion group (LO; n=28) for eight weeks intervention. Participants, care givers and laboratory assessor were blinded to the assignments (IRCT registry no: IRCT2012103111335N1). The compliance of participants in the analysis was appropriate (87.9%). Comparing changes throughout pre- and post-dose treatments indicated significant controls on carcinoembryonic antigen, cancer antigen-125 and alkaline phosphatase levels in the HO group (P<0.05). Our findings for the first time showed that regular onion administration could be effective for hepatic enzyme conveying adjuvant chemotherapy relevant toxicity and reducing the tumor markers in BC during doxorubicin-based chemotherapy.

Dietary resistant starch contained foods and breast cancer risk: a case-control study in northwest of Iran.

BACKGROUND: A protective effect of resistant starch (RS) containing foods on carcinogenesis has been shown from several lines of experimental evidence for gastrointestinal cancers. Therefore, we aimed to investigate the association between RS contained foods and breast cancer (BC) risk in a hospital-based, age- and origin- matched, case-control study. MATERIALS AND METHODS: A validated, semi-quantitative, food frequency questionnaire (FFQ) was completed by 306 women newly diagnosed with BC aged 25 to 65 years, and 309 healthy women as matched controls. Odds ratios (ORs) and 95% confidence intervals (95%CI) were estimated using conditional logistic regression models. RESULTS: Reduced BC risk was associated with the highest tertile of whole-wheat bread and boiled potato consumption with adjusted ORs at 0.34 (95%CI: 0.19-0.59) and 0.61 (95%CI: 0.37- 0.99), respectively. Among consumers of whole-wheat bread consumers were considered, the protective role of cereals remained relatively apparent at higher intakes level of fiber rich breads at adjusted models (OR=0.53, 95%CI: 0.28-1.01). Moreover, high intake of legumes was found out to be a significant protective dietary factor against risk of BC development with an OR of 0.01 (95%CI: 0.03-0.13). However, consumption of white bread and biscuits was positively related to BC risk. CONCLUSIONS: Our results show that certain RS containing foods, in particular whole wheat bread, legumes and boiled potato may reduce BC risk, whereas higher intake of white bread and biscuits may be related to increased BC risk.

Effects of raw red onion consumption on metabolic features in overweight or obese women with polycystic ovary syndrome: a randomized controlled clinical trial.

AIM: We aimed to evaluate the effects of raw red onion consumption on metabolic features in overweight and obese women with polycystic ovary syndrome. MATERIAL AND METHODS: In this randomized controlled clinical trial, the patients (n=54) were randomly allocated to the intervention group as 'high-onion' (raw red onions: 2 × 40-50 g/day if overweight and 2 × 50-60 g/day if obese) or to the control group as 'low-onion' (raw red onions: 2 × 10-15 g/day) along with limited liliaceous vegetables for 8 weeks. Body mass index, dietary record, and metabolic parameters (fasting blood sugar, triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and lipoprotein (a)) were evaluated in the follicular phase of the menstrual cycle at baseline and after 8 weeks. Hormonal variables (progesterone, prolactin, and 17-OH progesterone) were also measured at baseline. RESULTS: Onion significantly decreased the levels of total cholesterol within each group; however, these changes were stronger in the high-onion group (weighted mean differences [WMD]: -5.60 [95% confidence interval [CI]: -9.16, -2.03]; P=0.003) than in the low-onion group (WMD: -6.42 [95%CI: -11.97, -0.87]; P=0.025). Similarly, low-density lipoprotein cholesterol decreased significantly (WMD: -5.13 [95%CI: -9.46, -0.81); P=0.022) in the high-onion group, and (WMD: -2.90 [95%CI -5.57, -0.21]; P=0.035) in the low-onion group after treatment. The levels of fasting blood sugar, triglycerides, high-density lipoprotein cholesterol and lipoprotein (a) did not differ significantly after 8-week onion treatment. Adjustment for confounders did not make any significant changes in any of the parameters in post-treatment levels. CONCLUSION: Raw red onion consumption appears to be effective as a cholesterol-lowering food agent in women with polycystic ovary syndrome. However, further investigation is warranted.

Does grape seed oil improve inflammation and insulin resistance in overweight or obese women?

Grape seed oil (GSO) is reported to improve oxidative stress and lipid profile. However, the ameliorating effect of GSO on inflammation and insulin resistance has not being noticed so far. We aimed to examine the effects of GSO consumption on inflammation and insulin resistance in overweight or obese females. The subjects (n = 44) were randomly assigned into intervention group as "GSO" (consuming 15% of energy from GSO) and control group as sunflower oil "SFO" (consuming 15% of energy from SFO) through a weight loss diet for 8 weeks. Anthropometric measurements, dietary recall and fasting serum glucose, insulin, high sensitive C-reactive protein (hs-CRP) and tumor necrosis factor-alpha (TNF-α) were assessed before and after the intervention. Homeostatic model assessment of insulin resistance (HOMA-IR) scores, hs-CRP and TNF-α decreased in the GSO group. The hs-CRP was lower in GSO than the SFO group (p < 0.03). GSO consumption seems to improve inflammatory condition and insulin resistance in overweight/obese women.