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The effects of curcumin supplementation on oxidative stress, Sirtuin-1 and peroxisome proliferator activated receptor γ coactivator 1α gene expression in polycystic ovarian syndrome (PCOS) patients: A randomized placebo-controlled clinical trial.
Heshmati, J, Golab, F, Morvaridzadeh, M, Potter, E, Akbari-Fakhrabadi, M, Farsi, F, Tanbakooei, S, Shidfar, F
Diabetes & metabolic syndrome. 2020;(2):77-82
Abstract
BACKGROUND & AIMS Curcumin is a biologically active phytochemical ingredient found in turmeric and has antioxidant pharmacologic actions that may benefit patients with polycystic ovarian syndrome (PCOS). The aim in this trial was to evaluate the efficacy of curcumin supplementation on oxidative stress enzymes, sirtuin-1 (SIRT1) and Peroxisome proliferator activated receptor γ coactivator 1α (PGC1α) gene expression in PCOS patients. METHODS Seventy-two patients with PCOS were recruited for this randomized, double-blinded, clinical trial. Thirty-six patients received curcumin, 1500 mg (three times per day), and 36 patients received placebo for 3 months. Gene expression of SIRT1, PGC1α and serum activity of glutathione peroxidase (Gpx) and superoxide dismutase (SOD) enzymes were evaluated at the beginning of trial and at 3-month follow-up. RESULTS Sixty-seven patients with PCOS completed the trial. Curcumin supplementation significantly increased gene expression of PGC1α (p = 0.011) and activity of the Gpx enzyme (p = 0.045). Curcumin also non-significantly increased gene expression of SIRT1 and activity of the SOD enzyme. CONCLUSIONS Curcumin seems to be an efficient reducer of oxidative stress related complications in patients with PCOS. Further studies on curcumin should strengthen our findings.
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Status of Serum Copper, Magnesium, and Total Antioxidant Capacity in Patients with Polycystic Ovary Syndrome.
Kanafchian, M, Esmaeilzadeh, S, Mahjoub, S, Rahsepar, M, Ghasemi, M
Biological trace element research. 2020;(1):111-117
Abstract
This study evaluates serum copper and magnesium and total antioxidant capacity levels in PCOS patients. In this regard, the probable association of copper and magnesium with total antioxidant capacity (TAC) was investigated. In total, 150 women (60 PCOS patients and 90 healthy subjects) participated in this case-control study. PCOS was diagnosed according to the Rotterdam criteria (2003). Serum Cu, Mg, Ca, TAC, insulin levels, and insulin resistance indices were determined. Insulin was measured using ELISA methods. Serum Cu and Mg levels were measured by an atomic absorption spectrophotometer and the Xylidyl Blue method respectively. The correlations between the parameters were analyzed using the Spearman correlation test. Serum Cu level was significantly higher while TAC was significantly lower in the PCOS patients than those in the controls (p = 0.019 and p = 0.002 respectively). No significant difference was detected between the two groups in terms of serum Mg and Ca levels and Ca/Mg ratio. In insulin-resistant PCOS subjects, there was a negative correlation between Mg levels and homeostatic model assessment for insulin resistance (r = - 0.449, p = 0.006) but a positive correlation between Mg levels and quantitative insulin sensitivity check index (r = 0.480, p = 0.003). A negative correlation also existed between Mg levels and TAC in non-insulin-resistant PCOS patients (r = - 0.407, p = 0.04). According to the results, copper and magnesium seem to contribute to oxidative stress and insulin resistance in PCOS patients. Therefore, to prevent long-term metabolic complications in PCOS women, it is recommended that these elements be routinely monitored. Also, significantly lower levels of serum TAC in PCOS patients than in normal women may suggest increased oxidative stress in such patients.
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The effects of flaxseed supplementation on metabolic status in women with polycystic ovary syndrome: a randomized open-labeled controlled clinical trial.
Haidari, F, Banaei-Jahromi, N, Zakerkish, M, Ahmadi, K
Nutrition journal. 2020;(1):8
Abstract
BACKGROUND Polycystic Ovary Syndrome (PCOS) is known as the most common endocrine disorder of women in reproductive ages. With the increasing prevalence of PCOS in different countries, the use of herbal medicine as an alternative treatment is growing in these patients. This study aimed to evaluate the effects of flaxseed powder supplementation on metabolic biomarkers of patients with PCOS. METHODS This randomized open-labeled controlled clinical trial was conducted on 41 patients with PCOS. The participants were randomized to take either flaxseed powder (30 g/day) plus lifestyle modification or only lifestyle modification for 12 weeks. Anthropometric and biochemical evaluations were performed for all patients at the beginning and end of the study. RESULTS The flaxseed group showed a significant reduction in body weight, insulin concentration, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), Triglycerides (TG), high-sensitivity C-Reactive Protein (hs-CRP), and leptin and an increase in Quantitative Insulin-Sensitivity Check Index (QUICKI), High Density Lipoprotein (HDL), and adiponectin compared to the baseline (p < 0.05). Flaxseed supplementation also led to a significant reduction in insulin concentration, HOMA-IR, TG, hs-CRP, Interleukin 6 (IL- 6), and leptin and an increase in QUICKI, HDL, and adiponectin compared to the control group (p < 0.05). No significant changes were observed in other parameters. CONCLUSIONS Flaxseed supplementation plus lifestyle modification was more effective compared to lifestyle modification alone in biochemical and anthropometric variables in patients with PCOS. TRIAL REGISTRATION The trial protocol was approved by the Ethics Board at Ahvaz Jundishapur University of Medical Sciences and was registered at Iranian Registry of Clinical Trials (code: IRCT20120704010181N11).
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Zinc-alpha2-glycoprotein, dysglycaemia and insulin resistance: a systematic review and meta-analysis.
Pearsey, HM, Henson, J, Sargeant, JA, Davies, MJ, Khunti, K, Suzuki, T, Bowden-Davies, KA, Cuthbertson, DJ, Yates, TE
Reviews in endocrine & metabolic disorders. 2020;(4):569-575
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Abstract
To systematically review the current literature investigating associations between zinc-alpha2-glycoprotein (ZAG) and dysglycaemia (including type 2 diabetes (T2DM), poly-cystic-ovary syndrome (PCOS), pre-diabetes or insulin resistance). This included relationships between ZAG and continuous measures of insulin and glucose. Additionally, we performed a meta-analysis to estimate the extent that ZAG differs between individuals with or without dysglycaemia; whilst examining the potential influence of adiposity. A systematic search was performed on four databases for studies on circulating ZAG concentrations in adult human populations, comparing healthy controls to individuals with dysglycaemia. Key characteristics, including the mean ZAG concentrations (mg∙L-1), and any correlational statistics between ZAG and continuous measures of glucose, glycated haemoglobin (HbA1c) or insulin were extracted. Meta-analyses were performed to compare metabolically healthy controls to cases, and on studies that compared controls and cases considered overweight or obese (body mass index (BMI) ≥25 kg.m2). 1575 papers were identified and 14 studies (16 cohorts) were considered eligible for inclusion. Circulating ZAG was lower in individuals with dysglycaemia compared to metabolically healthy controls (-4.14 [-8.17, -0.11] mg.L-1; I2 = 98.5%; p < 0.001). When using data from only studies with overweight or obese groups with or without dysglycaemia (three studies (four cohorts); pooled n = 332), the difference in circulating ZAG was no longer significant (-0.30 [-3.67, 3.07] mg. L-1; I2 = 28.0%; p = 0.225). These data suggest that ZAG may be implicated in dysglycaemia, although there was significant heterogeneity across different studies and the mediating effect of adiposity cannot be excluded. Therefore, more research is needed before robust conclusions can be drawn.
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Effects of inositol and alpha lipoic acid combination for polycystic ovary syndrome: A protocol for systematic review and meta-analysis.
Lei, W, Gao, Y, Hu, S, Liu, D, Chen, Q
Medicine. 2020;(30):e20696
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BACKGROUND Polycystic ovary syndrome (PCOS), an intricate and multifactorial disease, has characteristics of diverse clinical, metabolic and endocrine disorder. It represents a primary cause of infertility in reproductive women, which seriously affects the physical and mental health of patients. Several small studies have indicated that inositol and alpha lipoic acid (ALA) supplementation can ameliorate the outcomes in terms of menstrual cyclicity, ovulation and hyperinsulinemia in PCOS women. However, there is a lack of sufficient evidence to affirm this practice. Consequently, we aim to objectively review and estimate the efficacy and safety of inositol plus ALA in adult women suffering from PCOS. METHODS AND ANALYSIS We will retrieve PubMed, EMBASE, The Web of Science, The Cochrane Library of Controlled Trials, Clinical Trials.gov, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP database), Wan-Fang database with no specific limitations on language. Simultaneously we will manually retrieve reference lists and grey literature to acquire potential eligibility. We will restrict our search to randomized controlled trials (RCTs) of inositol in combination with ALA for PCOS. Researchers will separately identify studies, extract data and evaluate the quality of studies. We will conduct risk of bias estimates, data synthesis and analysis using Review Manager 5.3 software. RESULTS AND CONCLUSION The study will comprehensively determine the effectiveness and safety of inositol conjunct with ALA therapy for PCOS. Meanwhile we intend to disseminate the final findings in a peer-reviewed journal to help patients, clinicians and health policymakers select treatment strategy of PCOS by providing high-quality evidence.
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Effects of curcumin on body weight, glycemic control and serum lipids in women with polycystic ovary syndrome: A randomized, double-blind, placebo-controlled trial.
Jamilian, M, Foroozanfard, F, Kavossian, E, Aghadavod, E, Shafabakhsh, R, Hoseini, A, Asemi, Z
Clinical nutrition ESPEN. 2020;:128-133
Abstract
OBJECTIVE The aim of this study was to evaluate the effect of curcumin on body weight, glycemic control and serum lipids in women suffering from polycystic ovary syndrome (PCOS). METHODS The current randomized, double-blinded, placebo-controlled clinical trial was performed on 60 subjects with PCOS, aged 18-40 years old. Subjects were randomly allocated to take 500 mg/day curcumin (n = 30) or placebo (n = 30) for 12 weeks. Glycemic control and serum lipids were measured at baseline and after the 12-week intervention. Using RT-PCR method, gene expression related to insulin and lipid metabolism was evaluated. RESULTS Curcumin significantly decreased weight (-0.8 ± 0.9 vs. -0.2 ± 0.8 kg, P = 0.03) and BMI (-0.3 ± 0.4 vs. -0.1 ± 0.3 kg/m2, P = 0.03). Curcumin, compared with the placebo, significantly reduced fasting glucose (β -2.63 mg/dL; 95% CI, -4.21, -1.05; P = 0.002), serum insulin (β -1.16 μIU/mL; 95% CI, -2.12, -0.19; P = 0.02), insulin resistance (β -0.26; 95% CI, -0.48, -0.03; P = 0.02), and significantly increased insulin sensitivity (β 0.006; 95% CI, 0.001, 0.01; P = 0.02). In addition, taking curcumin was associated with a significant reduction in total cholesterol (β -15.86 mg/dL; 95% CI, -24.48, -7.24; P = 0.001), LDL-cholesterol (β -16.09 mg/dL; 95% CI, -25.11, -7.06; P = 0.001) and total-/HDL-cholesterol ratio (β -0.62; 95% CI, -0.93, -0.30; P < 0.001), and a significant increase in HDL-cholesterol levels (β 2.14 mg/dL; 95% CI, 0.36, 3.92; P = 0.01) compared with the placebo. Additionally, curcumin administration up-regulated gene expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) (P = 0.03) and low-density lipoprotein receptor (LDLR) (P < 0.001) compared with the placebo. CONCLUSIONS Overall, curcumin administration for 12 weeks to women with PCOS had beneficial effects on body weight, glycemic control, serum lipids except triglycerides and VLDL-cholesterol levels, and gene expression of PPAR-γ and LDLR. Registered under Clinical Trials.gov Identifier no. http://www.irct.ir: IRCT20170513033941N50.
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Supervised exercise training and increased physical activity to reduce cardiovascular disease risk in women with polycystic ovary syndrome: study protocol for a randomized controlled feasibility trial.
Woodward, A, Broom, D, Dalton, C, Metwally, M, Klonizakis, M
Trials. 2020;(1):101
Abstract
BACKGROUND Polycystic ovary syndrome (PCOS) affects up to 20% of women and is characterised by higher amounts of visceral fat, obesity, insulin resistance, dyslipidemia and reproductive and cardiometabolic complications. Increased oxidised low-density lipoprotein (LDL) concentrations have been associated with an increased risk of cardiovascular disease (CVD)-related events. Oxidised LDL is rarely used as a marker for CVD risk in PCOS-related studies despite its widely accepted role in atherogenesis and the increased risk factors associated with PCOS. Additionally, prolonged periods of sedentary behaviour can negatively affect metabolic health. No studies have specifically examined the effects of reducing sedentary behaviour on CVD risk in PCOS with a lifestyle physical activity intervention. The aim of the current study is to measure the feasibility of a randomised controlled trial (RCT) examining the effects of supervised exercise and reducing sedentary behaviour in women with PCOS on CVD risk. METHODS/DESIGN A feasibility, exploratory RCT will be conducted. Fifty-one pre-menopausal females will be randomly allocated between an exercise group (EG), a lifestyle physical activity group (LPAG) and a control group. Participants in the EG will undertake a 12-week supervised aerobic exercise programme. The LPAG will aim to increase daily physical activity and reduce sedentary behaviour for 12 weeks. The control group will not take part in any intervention. Primary outcomes are feasibility and acceptability of the intervention and procedures. Secondary outcomes are oxidised LDL, aerobic fitness, blood lipid profile, fasting glucose and insulin, testosterone and inflammatory markers. DISCUSSION PCOS is associated with various increased risk factors for CVD, including hypertension, dyslipidemia, abdominal obesity, insulin resistance, and inflammation. Whether oxidised LDL has a role in this increased risk is not yet known. The present study aims to measure the feasibility of implementing structured exercise training and/or increased lifestyle physical activity in women with PCOS, so that a subsequent adequately powered RCT can be designed. The results from the study will be used to refine the interventions and determine the acceptability of the study design. A limitation is that some self-monitoring in the lifestyle physical activity group may not be reliable or replicable, for example inputting information about time spent cleaning/gardening. TRIAL REGISTRATION ClinicalTrials.gov, NCT03678714. Registered 20 September 2018.
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Is There An Advantage of Using Dingkun Pill () alone or in Combination with Diane-35 for Management of Polycystic Ovary Syndrome? A Randomized Controlled Trial.
Deng, Y, Wang, YF, Zhu, SY, Ma, X, Xue, W, Ma, RL, Sun, AJ
Chinese journal of integrative medicine. 2020;(12):883-889
Abstract
OBJECTIVE To evaluate the effects of Chinese medicine Dingkun Pill () alone or in combination with Diane-35 on patients with polycystic ovary syndrome (PCOS). METHODS This is a prospective randomized controlled trial conducted at Peking Union Medical College Hospital Beijing, China, from December 2016 to September 2017. Totally 117 PCOS patients were randomly assigned to the Dingkun Pill group (38 cases), Diane-35 group (40 cases), or combined group (39 cases). Patients in the Dingkun Pill group or Diane-35 group took daily 7 g of oral Dingkun Pill or 1 tablet of oral Diane-35, respectively, for 21 consecutive days followed by 7 drug-free days. And the combined group received a combination of Dingkun Pill and Diane-35. The treatment course was 3 months. Fasting plasma glucose and insulin, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), free fatty acids (FFA) and sex hormones were analyzed, quantitative insulin sensitivity check index (QUICKI) was calculated, and menstruation and acne scores were recorded at baseline and after 3-month treatment. RESULTS Compared with before treatment, QUICKI decreased significantly in the Dingkun Pill and combined groups after 3-month treatment (P<0.05); TC, LDL-C and FFA decreased significantly in the Dingkun Pill group (P<0.01), LDL-C also decreased obviously in the Diane-35 group (P<0.01), while TC increased significantly in the combined group (P<0.01), TG increased significantly in all groups (P<0.01); total testosterone (TT) and menstruation regularity was improved significantly in the Diane-35 and combined groups (P<0.01); acne scores were improved in all groups (P<0.01). After treatment, TC and FFA in the Dingkun Pill group were significantly lower than the Diane-35 group (P<0.05 or P<0.01); TT was lower and regular menstruation rate was higher in the Diane-35 and combined groups than the Dingkun Pill group (P<0.01), and no differences were observed between Diane-35 group and combined group (P>0.05). CONCLUSIONS Dingkun Pill showed better effects than Diane-35 in improving insulin sensitivity, lowering TC and FFA. Diane-35 was more efficient in regulating menstruation and lowering androgen than Dingkun Pill. Combination of Dingkun Pill and Diane-35 may be a better choice to regulate menstruation, lower androgens while improve glucose metabolism in PCOS patients. (Registered on ClinicalTrials.gov, registration No. NCT03264638).
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Cardiometabolic health in offspring of women with PCOS compared to healthy controls: a systematic review and individual participant data meta-analysis.
Gunning, MN, Sir Petermann, T, Crisosto, N, van Rijn, BB, de Wilde, MA, Christ, JP, Uiterwaal, CSPM, de Jager, W, Eijkemans, MJC, Kunselman, AR, et al
Human reproduction update. 2020;(1):103-117
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BACKGROUND Women diagnosed with polycystic ovary syndrome (PCOS) suffer from an unfavorable cardiometabolic risk profile, which is already established by child-bearing age. OBJECTIVE AND RATIONALE The aim of this systematic review along with an individual participant data meta-analysis is to evaluate whether cardiometabolic features in the offspring (females and males aged 1-18 years) of women with PCOS (OPCOS) are less favorable compared to the offspring of healthy controls. SEARCH METHODS PubMed, Embase and gray literature databases were searched by three authors independently (M.N.G., M.A.W and J.C.) (last updated on 1 February 2018). Relevant key terms such as 'offspring' and 'PCOS' were combined. Outcomes were age-specific standardized scores of various cardiometabolic parameters: BMI, blood pressure, glucose, insulin, lipid profile and the sum scores of various cardiometabolic features (metabolic sum score). Linear mixed models were used for analyses with standardized beta (β) as outcome. OUTCOMES Nine relevant observational studies could be identified, which jointly included 1367 children: OPCOS and controls, originating from the Netherlands, Chile and the USA. After excluding neonates, duplicate records and follow-up screenings, a total of 885 subjects remained. In adjusted analyses, we observed that OPCOS (n = 298) exhibited increased plasma levels of fasting insulin (β = 0.21(95%CI: 0.01-0.41), P = 0.05), insulin-resistance (β = 0.21(95%CI: 0.01-0.42), P = 0.04), triglycerides (β = 0.19(95%CI: 0.02-0.36), P = 0.03) and high-density lipoprotein (HDL)-cholesterol concentrations (β = 0.31(95%CI: 0.08-0.54), P < 0.01), but a reduced birthweight (β = -116(95%CI: -195 to 38), P < 0.01) compared to controls (n = 587). After correction for multiple testing, however, differences in insulin and triglycerides lost their statistical significance. Interaction tests for sex revealed differences between males and females when comparing OPCOS versus controls. A higher 2-hour fasting insulin was observed among female OPCOS versus female controls (estimated difference for females (βf) = 0.45(95%CI: 0.07 to 0.83)) compared to the estimated difference between males ((βm) = -0.20(95%CI: -0.58 to 0.19)), with interaction-test: P = 0.03. Low-density lipoprotein-cholesterol differences in OPCOS versus controls were lower among females (βf = -0.39(95%CI: -0.62 to 0.16)), but comparable between male OPCOS and male controls (βm = 0.27(95%CI: -0.03 to 0.57)), with interaction-test: P < 0.01. Total cholesterol differences in OPCOS versus controls were also lower in females compared to the difference in male OPCOS and male controls (βf = -0.31(95%CI: -0.57 to 0.06), βm = 0.28(95%CI: -0.01 to 0.56), interaction-test: P = 0.01). The difference in HDL-cholesterol among female OPCOS versus controls (βf = 0.53(95%CI: 0.18-0.88)) was larger compared to the estimated mean difference among OPCOS males and the male controls (βm = 0.13(95%CI: -0.05-0.31), interaction-test: P < 0.01). Interaction test in metabolic sum score revealed a significant difference between females (OPCOS versus controls) and males (OPCOS versus controls); however, sub analyses performed in both sexes separately did not reveal a difference among females (OPCOS versus controls: βf = -0.14(95%CI: -1.05 to 0.77)) or males (OPCOS versus controls: βm = 0.85(95%CI: -0.10 to 1.79)), with P-value < 0.01. WIDER IMPLICATIONS We observed subtle signs of altered cardiometabolic health in OPCOS. Therefore, the unfavorable cardiovascular profile of women with PCOS at childbearing age may-next to a genetic predisposition-influence the health of their offspring. Sensitivity analyses revealed that these differences were predominantly observed among female offspring aged between 1 and 18 years. Moreover, studies with minimal risk of bias should elucidate the influence of a PCOS diagnosis in mothers on both sexes during fetal development and subsequently during childhood.
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[Efficacy and mechanism of electroacupuncture on insulin resistant polycystic ovary syndrome].
Yu, LQ, Cao, LY, Xie, J, Shi, Y, Zhou, LY, He, TF, Chu, XY
Zhongguo zhen jiu = Chinese acupuncture & moxibustion. 2020;(4):379-83
Abstract
OBJECTIVE To explore the therapeutic effect and partial mechanism of electroacupuncture (EA) for patients with insulin resistance (IR) polycystic ovary syndrome (PCOS). METHODS Seventy patients with IR-PCOS were randomly divided into an EA group (36 cases, 5 cases dropped off) and a medication group (34 cases, 4 cases dropped off). The patients in the medication group were treated with oral administration of metformin hydrochloride, 500 mg each time, twice a day. The patients in the EA group were treated with EA (continuous wave, 2 Hz of frequency) at Zusanli (ST 36), Zhongwan (CV 12), Qihai (CV 6), Yishu (EX-B 3), Shenshu (BL 23), Pishu (BL 20), Ciliao (BL 32) for 30 min, three times a week. One menstrual cycle or 4 weeks were taken as a course of treatment, and 3 continuous courses were given. The follow-up was 3 months. The lipid metabolism indexes of triacylglycerol (TG), total cholesterol (TC), high-density lipoprotein (HDL) and low-density lipoprotein (LDL), homeostasis model assessment-insulin resistance index (HOMA-IR) and testosterone (T) in serum were compared before and after treatment, and the clinical effects of the two groups were evaluated during the follow-up. RESULTS The total effective rate was 67.7% (21/31) in the EA group and 60.0% (18/30) in the medication group, with no significant difference between the two groups (P>0.05). After treatment, the levels of serum T, HOMA-IR, LDL, TG and TC were decreased significantly in the two groups (P<0.01, P<0.05), and HDL was increased significantly (P<0.01); the levels of TC in the EA group after treatment was lower than that in the medication group (P<0.05). CONCLUSION EA may adjust some dyslipidemia in patients to correct IR and improve endocrine disorder of PCOS, which had superior/similar effects to metformin.