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Ketogenic diet for human diseases: the underlying mechanisms and potential for clinical implementations.
Zhu, H, Bi, D, Zhang, Y, Kong, C, Du, J, Wu, X, Wei, Q, Qin, H
Signal transduction and targeted therapy. 2022;(1):11
Abstract
The ketogenic diet (KD) is a high-fat, adequate-protein, and very-low-carbohydrate diet regimen that mimics the metabolism of the fasting state to induce the production of ketone bodies. The KD has long been established as a remarkably successful dietary approach for the treatment of intractable epilepsy and has increasingly garnered research attention rapidly in the past decade, subject to emerging evidence of the promising therapeutic potential of the KD for various diseases, besides epilepsy, from obesity to malignancies. In this review, we summarize the experimental and/or clinical evidence of the efficacy and safety of the KD in different diseases, and discuss the possible mechanisms of action based on recent advances in understanding the influence of the KD at the cellular and molecular levels. We emphasize that the KD may function through multiple mechanisms, which remain to be further elucidated. The challenges and future directions for the clinical implementation of the KD in the treatment of a spectrum of diseases have been discussed. We suggest that, with encouraging evidence of therapeutic effects and increasing insights into the mechanisms of action, randomized controlled trials should be conducted to elucidate a foundation for the clinical use of the KD.
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Physical Activity and Cardiometabolic Risk Factor Clustering in Young Adults with Obesity.
Dipietro, L, Zhang, Y, Mavredes, M, Simmens, SJ, Whiteley, JA, Hayman, LL, Faro, J, Malin, SK, Winston, G, Napolitano, MA
Medicine and science in sports and exercise. 2020;(5):1050-1056
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INTRODUCTION There is a paucity of information on the clustering of cardiometabolic risk factors in young adults and how this clustering may vary based on whether or not they perform sufficient levels of physical activity. METHODS We analyzed baseline data from 346 young adults (23.3 ± 4.4 yr) participating in the Healthy Body Healthy U clinical trial from 2015 to 2018. Cardiometabolic risk factors were measured according to standard procedures and moderate- to vigorous-intensity physical activity (MVPA) was determined by accelerometry. A cardiometabolic clustering score (ranging from 0 to 5) was created from five biomarkers according to whether or not a standard clinical risk cut point was exceeded (0, no; 1, yes): abdominal circumference (>102 cm (men) or >88 cm (women)), hemoglobin A1c (≥5.7%), HDL cholesterol (<40 mg·dL (men) or <50 mg·dL (women)), systolic blood pressure (≥130 mm Hg), and diastolic blood pressure (≥85 mm Hg). Cardiometabolic dysregulation (CD) was defined as a cardiometabolic clustering score ≥3. Multiple logistic regression determined the independent association between level of MVPA and CD, while adjusting for sex, race/ethnicity, sedentary time, and smoking. RESULTS The prevalence of CD was 18% (22% in men, 17% in women). We observed a nonlinear graded association between MVPA and CD. Participants performing 150-300 min·wk of MVPA significantly lowered their odds of CD by 66% (odds ratio, 0.34; 95% confidence interval, 0.16-0.75), whereas those exceeding 300 min·wk lowered their odds by 61% (odds ratio, 0.39; 95% confidence interval, 0.18-0.86) compared with those performing <150 min·wk, independent of obesity and the other covariables. CONCLUSION Recommended levels of moderate-intensity physical activity is significantly associated with lower odds of CD and thus may prevent or diminish the need for expensive pharmaceutical treatment over the remainder of the life-span.
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Acupoint catgut embedding for obesity: A protocol of systematic review.
Huang, W, Chen, X, Zhang, Y, Wang, L, Wang, J, Zhang, Y, Wei, D, Zhou, Z
Medicine. 2020;(51):e23728
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BACKGROUND Obesity is a chronic metabolic disease in which patients are overweight due to the excessive accumulation of fat in the body. As a subtype of acupuncture, catgut embedding at acupoints has increased in clinical application for obesity. The aim of this study is to evaluate the effectiveness and safety of acupoint catgut embedding therapy for simple obesity. METHODS AND ANALYSIS Electronic searches of the Cochrane Library, PubMed, Springer Medline, EMBASE, Web of Science, China National Knowledge Infrastructure (CNKI), Wan-Fang Data (WANFANG), Chinese Biomedical Literature Database (CBM), and Chinese Scientific Journal Database (VIP databases) will be performed. The Chinese Clinical Trial Registry Center and the ClinicalTrials.gov registry will also be searched for ongoing trials. Databases will be searched from inception to August 2020.Randomized controlled clinical trials (RCTs) will be included if acupoint catgut embedding was evaluated as the sole treatment (diet or exercise therapy as the control group will be allowed) for simple obesity. The primary outcomes will consist of the improvement rate and reduction in body weight (BW). The secondary outcomes will include body mass index (BMI), waist circumference (WC), fat percentage (F %) and adverse effects. Two reviewers will undertake the study selection, data extraction and assessments of study quality. After screening the studies, the quality of the included studies will be assessed according to the quality criteria specified by the Cochrane Handbook for Systematic Reviews of Interventions (version 5.1.0). Meta-analysis will be performed by RevMan 5.3 software. RESULTS According to the data of improvement rate and reduction in BW, BMI, WC, and F %, this study will provide an evidence-based review of acupoint catgut embedding therapy for simply. CONCLUSIONS This systematic review will present the current evidence for acupoint catgut embedding therapy for obesity. ETHICS AND DISSEMINATION Ethical approval is not necessary since this protocol is only for systematic review and does not involve privacy data. The findings of this study will be disseminated electronically through a peer-review publication or presented at a relevant conference. TRIAL REGISTRATION NUMBER INPLASY2020110045.
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The effect of green-coffee extract supplementation on obesity: A systematic review and dose-response meta-analysis of randomized controlled trials.
Gorji, Z, Varkaneh, HK, Talaei, S, Nazary-Vannani, A, Clark, CCT, Fatahi, S, Rahmani, J, Salamat, S, Zhang, Y
Phytomedicine : international journal of phytotherapy and phytopharmacology. 2019;:153018
Abstract
BACKGROUND Given that the most recent systematic review investigating Green-Coffee Extract (GCE) as a weight loss facilitator was nearly a decade ago and that the authors reported there no consensus on the effect of GCE/CGA (Chlorogenic acids) on body composition indices, a comprehensive systematic review and dose-response meta-analysis of all available randomized controlled trial (RCTs) was undertaken to examine the effect of GCE and CGA intervention on body weight (BW), body mass index (BMI) and waist circumference (WC) in adults. METHODS We conducted a systematic search of all available randomized controlled trials (RCTs) performed up to June 2019 in the following electronic databases: PubMed, Scopus and Google Scholar. RCTs that investigated the effect GCE/CGA Supplementation on BW, BMI and WC in adults were included for final analysis. The pooled weight mean difference (WMD) of included studies was estimated using a random-effects model. RESULTS A total of 13 articles with 16 RCTs were included in the meta-analysis. Results revealed significant reduction in BMI (WMD: -0.403 kg/m2, 95% CI: -0.800, -0.005, p = 0.047) and no significant change in BW (WMD: -0.585 kg, 95% CI: -1.498, 0.329, p = 0.210) and WC (WMD: -0.847 cm, 95% CI: -1.764, 0.071, p = 0.070). In the subgroup analysis, studies that were conducted on baseline BMI ≥25 kg/m2 revealed a significant greater reduction in body weight and BMI than those performed on baseline BMI <25 kg/m2. Moreover, short supplementation periods of less than 4 weeks had no effect. CONCLUSION The results of current meta-analysis study support the use of GCE supplementation for the improvement of obesity indices, with sub-group analysis highlighting greater improvements in individuals with a starting BMI ≥25 kg/m2.
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Possible anti-obesity effects of phytosterols and phytostanols supplementation in humans: A systematic review and dose-response meta-analysis of randomized controlled trials.
Ghaedi, E, Varkaneh, HK, Rahmani, J, Mousavi, SM, Mohammadi, H, Fatahi, S, Pantovic, A, Darooghegi Mofrad, M, Zhang, Y
Phytotherapy research : PTR. 2019;(5):1246-1257
Abstract
Present meta-analysis investigates the effects of phytosterols and phytostanol (PS) supplementation on anthropometric indices, using data from randomized controlled trials. We performed a systematic search in the databases: PubMed, Scopus, Cochran, and Web of Science. Weighted mean difference (WMD) with 95% confidence intervals (CIs) were presented. Overall, 79 randomized controlled trials investigated the effects of PS on anthropometric indices. Meta-analysis results did not reveal any significant effect of PS supplementation on weight (66 trials-WMD: -0.083 kg; CI [-0.233, 0.066]; I2 = 42.5%), percentage fat mass (6 trials-WMD: -0.090%; CI [-0.789, 0.610]; I2 = 0.0%), and waist circumference (WC; 5 trials-WMD: -0.039 cm; CI [-0.452, 0.374]; I2 = 0.0%). However, body mass index (BMI) significantly decreased after PS supplementation (39 trials-WMD: -0.063 kg/m2, p = 0.024, I2 = 25.1%). Subgroup analyses showed that PS supplementation in subjects with baseline BMI ≥25 and hyperlipidemic significantly decreased body weight and BMI. The overall results showed that although PS supplementation did not affect anthropometric indices (except BMI), baseline status regarding BMI and hyperlipidemia and also dose and duration could be contributing factors for favorable effects.
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A randomized clinical trial of exercise during pregnancy to prevent gestational diabetes mellitus and improve pregnancy outcome in overweight and obese pregnant women.
Wang, C, Wei, Y, Zhang, X, Zhang, Y, Xu, Q, Sun, Y, Su, S, Zhang, L, Liu, C, Feng, Y, et al
American journal of obstetrics and gynecology. 2017;(4):340-351
Abstract
BACKGROUND Obesity and being overweight are becoming epidemic, and indeed, the proportion of such women of reproductive age has increased in recent times. Being overweight or obese prior to pregnancy is a risk factor for gestational diabetes mellitus, and increases the risk of adverse pregnancy outcome for both mothers and their offspring. Furthermore, the combination of gestational diabetes mellitus with obesity/overweight status may increase the risk of adverse pregnancy outcome attributable to either factor alone. Regular exercise has the potential to reduce the risk of developing gestational diabetes mellitus and can be used during pregnancy; however, its efficacy remain controversial. At present, most exercise training interventions are implemented on Caucasian women and in the second trimester, and there is a paucity of studies focusing on overweight/obese pregnant women. OBJECTIVE We sought to test the efficacy of regular exercise in early pregnancy to prevent gestational diabetes mellitus in Chinese overweight/obese pregnant women. STUDY DESIGN This was a prospective randomized clinical trial in which nonsmoking women age >18 years with a singleton pregnancy who met the criteria for overweight/obese status (body mass index 24≤28 kg/m2) and had an uncomplicated pregnancy at <12+6 weeks of gestation were randomly allocated to either exercise or a control group. Patients did not have contraindications to physical activity. Patients allocated to the exercise group were assigned to exercise 3 times per week (at least 30 min/session with a rating of perceived exertion between 12-14) via a cycling program begun within 3 days of randomization until 37 weeks of gestation. Those in the control group continued their usual daily activities. Both groups received standard prenatal care, albeit without special dietary recommendations. The primary outcome was incidence of gestational diabetes mellitus. RESULTS From December 2014 through July 2016, 300 singleton women at 10 weeks' gestational age and with a mean prepregnancy body mass index of 26.78 ± 2.75 kg/m2 were recruited. They were randomized into an exercise group (n = 150) or a control group (n = 150). In all, 39 (26.0%) and 38 (25.3%) participants were obese in each group, respectively. Women randomized to the exercise group had a significantly lower incidence of gestational diabetes mellitus (22.0% vs 40.6%; P < .001). These women also had significantly less gestational weight gain by 25 gestational weeks (4.08 ± 3.02 vs 5.92 ± 2.58 kg; P < .001) and at the end of pregnancy (8.38 ± 3.65 vs 10.47 ± 3.33 kg; P < .001), and reduced insulin resistance levels (2.92 ± 1.27 vs 3.38 ± 2.00; P = .033) at 25 gestational weeks. Other secondary outcomes, including gestational weight gain between 25-36 gestational weeks (4.55 ± 2.06 vs 4.59 ± 2.31 kg; P = .9), insulin resistance levels at 36 gestational weeks (3.56 ± 1.89 vs 4.07 ± 2.33; P = .1), hypertensive disorders of pregnancy (17.0% vs 19.3%; odds ratio, 0.854; 95% confidence interval, 0.434-2.683; P = .6), cesarean delivery (except for scar uterus) (29.5% vs 32.5%; odds ratio, 0.869; 95% confidence interval, 0.494-1.529; P = .6), mean gestational age at birth (39.02 ± 1.29 vs 38.89 ± 1.37 weeks' gestation; P = .5); preterm birth (2.7% vs 4.4%, odds ratio, 0.600; 95% confidence interval, 0.140-2.573; P = .5), macrosomia (defined as birthweight >4000 g) (6.3% vs 9.6%; odds ratio, 0.624; 95% confidence interval, 0.233-1.673; P = .3), and large-for-gestational-age infants (14.3% vs 22.8%; odds ratio, 0.564; 95% confidence interval, 0.284-1.121; P = .1) were also lower in the exercise group compared to the control group, but without significant difference. However, infants born to women following the exercise intervention had a significantly lower birthweight compared with those born to women allocated to the control group (3345.27 ± 397.07 vs 3457.46 ± 446.00 g; P = .049). CONCLUSION Cycling exercise initiated early in pregnancy and performed at least 30 minutes, 3 times per week, is associated with a significant reduction in the frequency of gestational diabetes mellitus in overweight/obese pregnant women. And this effect is very relevant to that exercise at the beginning of pregnancy decreases the gestational weight gain before the mid-second trimester. Furthermore, there was no evidence that the exercise prescribed in this study increased the risk of preterm birth or reduced the mean gestational age at birth.
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Effect of green tea supplementation on blood pressure among overweight and obese adults: a systematic review and meta-analysis.
Li, G, Zhang, Y, Thabane, L, Mbuagbaw, L, Liu, A, Levine, MA, Holbrook, A
Journal of hypertension. 2015;(2):243-54
Abstract
BACKGROUND Emerging randomized controlled trials (RCTs) investigating the effect of green tea or green tea extract (GTE) supplementation on blood pressure (BP) among overweight and obese adults reported inconsistent findings. OBJECTIVE To conduct a systematic review and meta-analysis to clarify the efficacy of green tea or GTE on BP among overweight and obese adults. METHODS Electronic databases, conference proceedings and gray literature were searched systematically to include parallel and cross-over RCTs examining the efficacy of green tea or GTE on BP compared with placebo. Data were meta-analyzed using a random-effects model, to compare the mean difference of the change in BP from baseline in the intervention and the placebo groups. RESULTS Fourteen RCTs with 971 participants (47% women) were pooled for analysis. Green tea or GTE produced a significant effect on both SBP (mean difference -1.42 mmHg, 95% confidence interval -2.47 to -0.36, P = 0.008; I = 52%, P = 0.01 for heterogeneity) and DBP (mean difference -1.25 mmHg, 95% confidence interval -2.32 to -0.19, P = 0.02; I = 74%, P < 0.001 for heterogeneity), compared with placebo. The quality of evidence across studies was low. Similar results were found in subgroup and sensitivity analyses. CONCLUSION Among overweight and obese adults, green tea or GTE supplementation is found to cause a small but significant reduction in BP. More high-quality RCTs with large sample sizes are needed to further confirm the efficacy on BP and make strong recommendations for green tea or GTE supplementation among the overweight and obese adults.
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Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index.
Wen, W, Zheng, W, Okada, Y, Takeuchi, F, Tabara, Y, Hwang, JY, Dorajoo, R, Li, H, Tsai, FJ, Yang, X, et al
Human molecular genetics. 2014;(20):5492-504
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Recent genetic association studies have identified 55 genetic loci associated with obesity or body mass index (BMI). The vast majority, 51 loci, however, were identified in European-ancestry populations. We conducted a meta-analysis of associations between BMI and ∼2.5 million genotyped or imputed single nucleotide polymorphisms among 86 757 individuals of Asian ancestry, followed by in silico and de novo replication among 7488-47 352 additional Asian-ancestry individuals. We identified four novel BMI-associated loci near the KCNQ1 (rs2237892, P = 9.29 × 10(-13)), ALDH2/MYL2 (rs671, P = 3.40 × 10(-11); rs12229654, P = 4.56 × 10(-9)), ITIH4 (rs2535633, P = 1.77 × 10(-10)) and NT5C2 (rs11191580, P = 3.83 × 10(-8)) genes. The association of BMI with rs2237892, rs671 and rs12229654 was significantly stronger among men than among women. Of the 51 BMI-associated loci initially identified in European-ancestry populations, we confirmed eight loci at the genome-wide significance level (P < 5.0 × 10(-8)) and an additional 14 at P < 1.0 × 10(-3) with the same direction of effect as reported previously. Findings from this analysis expand our knowledge of the genetic basis of obesity.
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Effect of green tea supplementation on blood pressure among overweight and obese adults: a protocol for a systematic review.
Li, G, Zhang, Y, Mbuagbaw, L, Holbrook, A, Levine, MA, Thabane, L
BMJ open. 2014;(4):e004971
Abstract
INTRODUCTION Emerging randomised controlled trials (RCTs) exploring the effect of green tea (GT) supplementation or GT extract (GTE) on blood pressure (BP) among overweight and obese adults yielded inconclusive results. We aim to conduct a systematic review to summarise the evidence of RCTs until now, to clarify the efficacy of GT supplementation or GTE in BP in overweight and obese populations. METHODS AND ANALYSIS The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and ClinicalTrials.gov will be searched to retrieve potential RCTs. Unpublished studies will be identified by searching the abstract books or websites of the three major conference proceedings: the International Society of Hypertension, the Nutrition & Health Conference and the World Congress of Nutrition and Health. A random-effects meta-analysis will be performed to pool the mean difference for the change in BP from baseline (ie, postintervention BP minus baseline BP) between intervention groups and placebo groups of the included studies, presenting the pooled results with 95% CIs. Subgroups analyses will be conducted according to different doses of GT or GTE, trial duration, geographic regions, overweight versus obese participants, and participants with versus without change in body weight after intervention. Sensitivity analysis will be performed by excluding studies classified as having a high risk of bias, applying a fixed-effects model, using the postintervention BP for analyses and excluding trials with non-study cointerventions. ETHICS AND DISSEMINATION This systematic review will be published in a peer-reviewed journal. It will be disseminated electronically and in print. Summarising the RCT evidence to clarify the efficacy in BP among overweight and obese adults will aid in making the dietary recommendation of GT and improving the clinical management of hypertension. TRIAL REGISTRATION NUMBER PROSPERO CRD42014007273.
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Safety and antioxidant activity of a pomegranate ellagitannin-enriched polyphenol dietary supplement in overweight individuals with increased waist size.
Heber, D, Seeram, NP, Wyatt, H, Henning, SM, Zhang, Y, Ogden, LG, Dreher, M, Hill, JO
Journal of agricultural and food chemistry. 2007;(24):10050-4
Abstract
The consumption of pomegranate juice (PJ), a rich source of antioxidant polyphenols, has grown tremendously due to its reported health benefits. Pomegranate extracts, which incorporate the major antioxidants found in pomegranates, namely, ellagitannins, have been developed as botanical dietary supplements to provide an alternative convenient form for consuming the bioactive polyphenols found in PJ. Despite the commercial availability of pomegranate extract dietary supplements, there have been no studies evaluating their safety in human subjects. A pomegranate ellagitannin-enriched polyphenol extract (POMx) was prepared for dietary supplement use and evaluated in two pilot clinical studies. Study 1 was designed for safety assessment in 64 overweight individuals with increased waist size. The subjects consumed either one or two POMx capsules per day providing 710 mg (435 mg of gallic acid equivalents, GAEs) or 1420 mg (870 mg of GAEs) of extracts, respectively, and placebo (0 mg of GAEs). Safety laboratory determinations, including complete blood count (CBC), chemistry, and urinalysis, were made at each of three visits. Study 2 was designed for antioxidant activity assessment in 22 overweight subjects by administration of two POMx capsules per day providing 1000 mg (610 mg of GAEs) of extract versus baseline measurements. Measurement of antioxidant activity as evidenced by thiobarbituric acid reactive substances (TBARS) in plasma were measured before and after POMx supplementation. There was evidence of antioxidant activity through a significant reduction in TBARS linked with cardiovascular disease risk. There were no serious adverse events in any subject studied at either site. These studies demonstrate the safety of a pomegranate ellagitannin-enriched polyphenol dietary supplement in humans and provide evidence of antioxidant activity in humans.