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Effects of acute sleep loss on leptin, ghrelin, and adiponectin in adults with healthy weight and obesity: A laboratory study.
van Egmond, LT, Meth, EMS, Engström, J, Ilemosoglou, M, Keller, JA, Vogel, H, Benedict, C
Obesity (Silver Spring, Md.). 2023;31(3):635-641
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A lack of sleep may be a risk factor for weight gain. Leptin is an adipocyte-derived hormone that activates satiety networks within the brain. Ghrelin, as opposed to leptin, is mainly produced by the stomach and it acts as a hunger hormone, signalling fuel status to the central nervous system. Some studies have found either no alterations or higher leptin and lower ghrelin blood levels following experimental sleep deprivation. The aim of this study was to investigate whether blood concentrations of leptin, ghrelin, and adiponectin are affected by acute total sleep deprivation in a sex- and weight-specific manner. This study is a laboratory study based on blood samples from 44 participants, mainly university students. Results show that: - acute total sleep deprivation is linked to lower serum levels of the adipokine leptin and higher blood levels of ghrelin. - following sleep deprivation, serum adiponectin levels were elevated. - the drop in serum leptin was larger in women after total sleep deprivation; however, there wasn’t a significant association between biological sex and experimental condition. - the increase in blood levels of adiponectin was slightly more pronounced among women, whereas there weren’t any differences in the effects of sleep loss on plasma ghrelin. Authors conclude that acute total sleep deprivation shifts the endocrine balance from the satiety hormone leptin toward the hunger-promoting hormone ghrelin. However, further investigation in larger samples focusing on their findings linked to sex- and weight-specific differences in leptin, ghrelin, and adiponectin are needed.
Expert Review
Conflicts of interest:
None
Take Home Message:
Sleep deprivation may shift the balance of appetite controlling hormones causing an increase in hunger and decreased satiety and therefore resulting in increased food intake. These changes may be more pronounced in biological females.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
Sleep deprivation may contribute to weight gain and obesity through its effect on the hormonal pathways promoting hunger and satiety. Research has also linked chronic sleep loss with an increase in the brain reward response to food, thus driving an increase in daily food intake. Leptin and ghrelin are hormones involved in the control of food intake. Some research has associated alterations in these hormones following sleep loss, whilst others have not.
This study aimed to investigate whether biological sex and weight status affect fasting serum levels of leptin, ghrelin and adiponectin following chronic sleep deprivation in a supervised laboratory setting.
Methods
This randomised crossover design study included n=44 mixed sex participants with a mean age of 24.9 years. A total of 19 of the participants were classed as obese, with the remaining n= 25 participants were considered normal weight. Participants completed 2 nights in experimental sessions under continuously supervised conditions in a laboratory. One night was spent awake and the other asleep. Fasting blood samples were taken the morning after each session to measure levels of leptin, ghrelin and adiponectin.
Results
Serum levels of leptin after one night’s sleep loss were around 7% lower than those measured after sleep (17.3 = +/-2.6 vs 18.6 +/- 2.8 ng/mL, p = 0.037). Adjustments using sex-stratified analysis showed significantly lower levels of serum leptin in women (25.8 +/_4.3 vs 28.1 +/_ 4.7 ng/mL, p = 0.030) but not for men (10.1 +/_ 2.4 vs 10.6 +/_ 2.3 ng/mL, p = 0.458). However, when comparing individual participant differences between sleep and wake sessions, the results were not significant. Additionally, no significant differences were found between normal weight and obese participants.
Higher levels of ghrelin were found following sleep deprivation in both sexes and weight sub-groups (839.4 +/-77.5 vs 741.4+/-63.2 pg/mL, p= 0.003). Adiponectin was also found to be elevated in all participants regardless of biological sex or weight status (7.5 +/- 0.6 vs 6.8 +/- 0.6ug/mL, p= 0.003). However, ghrelin was observed to increase slightly more in participants with obesity, whereas elevations in adiponectin were slightly greater in those of normal weight.
Conclusion
In this study, sleep loss was associated with lowered levels of leptin and higher levels of ghrelin. Analysis between biological sexes indicated that there may be a greater decrease in leptin in females. Serum levels of adiponectin were also found to be elevated after sleep deprivation for both sexes with a slightly larger increase in women. These changes may result in increased hunger and food intake and decreased satiety. No significant differences were found between normal weight and obese participants.
Notes: The authors reported no conflicts of interest.
Clinical practice applications:
Sleep deprivation may lead to lower levels of leptin in both sexes with a greater decrease for females. Ghrelin and adiponectin levels may be increased in both men and women after sleep loss with a slightly larger increase in adiponectin for women. This could lead to an increase in appetite, food consumption and therefore weight gain, particularly in women.
Considerations for future research:
- Larger studies are needed to investigate sex and weight status related differences in serum levels of ghrelin, leptin and adiponectin.
- It may be beneficial for blood samples to be taken at different points during the day to allow for fluctuations in hormone levels.
- Food intake should be measured to monitor any increases in food intake.
Abstract
OBJECTIVE This study investigated whether blood concentrations of leptin, ghrelin, and adiponectin are affected by acute total sleep deprivation in a sex- and weight-specific manner. METHODS A total of 44 participants (mean age 24.9 years; 20 women; 19 with obesity) participated in a crossover design, including one night of sleep deprivation and one night of sleep in the laboratory. After each night, fasting blood was collected. RESULTS After sleep deprivation, fasting levels of leptin were lower (mean [SE], vs. sleep: 17.3 [2.6] vs. 18.6 [2.8] ng/mL), whereas those of ghrelin and adiponectin were higher (839.4 [77.5] vs. 741.4 [63.2] pg/mL and 7.5 [0.6] vs. 6.8 [0.6] μg/mL, respectively; all p < 0.05). The changes in leptin and adiponectin following sleep loss were more pronounced among women. Furthermore, the ghrelin increase was stronger among those with obesity after sleep loss. Finally, the sleep loss-induced increase in adiponectin was more marked among normal-weight participants. CONCLUSIONS Acute sleep deprivation reduces blood concentrations of the satiety hormone leptin. With increased blood concentrations of ghrelin and adiponectin, such endocrine changes may facilitate weight gain if persisting over extended periods of sleep loss. The observed sex- and weight-specific differences in leptin, ghrelin, and adiponectin call for further investigation.
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Effects of lifestyle interventions on cardiovascular risk factors in South Asians: a systematic review and meta-analysis.
Limbachia, J, Ajmeri, M, Keating, BJ, de Souza, RJ, Anand, SS
BMJ open. 2022;12(12):e059666
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The prevalence of cardiovascular disease (CVD) and associated mortality risk is high in the South Asian population in western countries. Regular physical activity and a healthy diet may modify the risk factors of CVD, such as abdominal fat, high cholesterol, and blood sugar irregularities. This systematic review and meta-analysis included thirty-five randomised controlled trials to evaluate the effectiveness of diet, physical activity interventions or a combination of diet and physical activity interventions on CVD risk factors and compared it against usual care. Combining diet and physical activity interventions reduced CVD risk factors such as systolic and diastolic blood pressure, BMI, weight, waist circumference and fasting plasma glucose (FPG). Dietary interventions reduced diastolic blood pressure, triglycerides, low-density lipoprotein cholesterol, BMI, weight and FPG. Physical activity modifications improved diastolic and systolic blood pressure and high-density lipoprotein cholesterol. Healthcare professionals can use the study results to understand how tailored diet and physical activity modifications improve the CVD risk factors in South Asians. However, further robust studies are required as most of these evidences were of moderate quality and lacked clinical significance.
Abstract
BACKGROUND The cardiovascular disease (CVD) burden among South Asians is high. Lifestyle interventions have been effective in the primary prevention of CVD, but this has not been replicated, through a synthesis of randomised trials, in South Asians. METHODS Four electronic databases (MEDLINE, Embase, CENTRAL and CINAHL), two clinical trial registries and references of included articles were searched through June 2022 (featuring ≥90% South Asian participants). Random-effects pairwise meta-analyses were performed, and heterogeneity was quantified with the I2 statistic. The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) framework was used to report on the quality of evidence (International Prospective Register of Systematic Reviews registration (PROSPERO). RESULTS Thirty-five studies were included. Twelve tested diet and physical activity interventions; 18 tested diet alone; and 5 tested physical activity alone. All reported effects of the intervention(s) on at least one established risk factor for CVD, including blood pressure (systolic blood pressure (SBP), diastolic blood pressure (DBP) and blood lipids (high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc) or triglycerides). No trials reported clinical CVD. There is moderate-quality evidence that diet and physical activity interventions improve SBP (mean difference (MD) -2.72 mm Hg, 95% CI -4.11 to -1.33) and DBP (MD -1.53 mm Hg, 95% CI -2.57 to -0.48); high-quality to moderate-quality evidence that diet-only interventions improve DBP (MD -2.05 mm Hg, 95% CI -2.93 to -1.16) and blood lipids (triglycerides (MD -0.10 mmol/L, 95% CI -0.14 to -0.06) and LDLc (MD -0.19 mmol/L, 95% CI -0.32 to -0.06)); and moderate-quality evidence that physical activity-only interventions improve SBP (MD -9.7 mm Hg, 95% CI -11.05 to -8.35), DBP (MD -7.29 mm Hg, 95% CI -8.42 to -6.16) and HDLc (MD 0.08 mmol/L, 95% CI 0.04 to 0.11) compared with usual care. CONCLUSIONS Lifestyle interventions improve blood pressure and blood lipid profiles in adult South Asians at risk of CVD. Tailored interventions should be used to modify cardiovascular risk factors in this at-risk group. PROSPERO REGISTRATION NUMBER CRD42018090419.
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Cardiometabolic Risk Factors and Incident Cardiovascular Disease Events in Women vs Men With Type 1 Diabetes.
Braffett, BH, Bebu, I, El Ghormli, L, Cowie, CC, Sivitz, WI, Pop-Busui, R, Larkin, ME, Gubitosi-Klug, RA, Nathan, DM, Lachin, JM, et al
JAMA network open. 2022;5(9):e2230710
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In the general population, women have a lower absolute risk of cardiovascular disease (CVD) compared with men. However, among individuals with type 1 or type 2 diabetes, the relative risk of CVD is similar or higher in women compared with men. The aim of this study was to assess sex differences in achieving recommended CVD risk management targets and associations with CVD events. This is a cohort study which included a total of 1441 (men n= 736) participants with type 1 diabetes. Results show that the prevalence and mean levels of most cardiometabolic risk factors (except for pulse rate and haemoglobin A1c) were consistent with a less atherogenic profile among women compared with men. Furthermore, achieving treatment targets for blood pressure, lipids, and glucose was associated with significantly decreased risk of CVD in both women and men. Authors conclude that their findings argue for a recalibration of CVD risk factor stratification in revised clinical care guidelines and therapeutic recommendations by sex for individuals with type 1 diabetes.
Abstract
IMPORTANCE The lower risk of cardiovascular disease (CVD) among women compared with men in the general population may be diminished among those with diabetes. OBJECTIVE To evaluate cardiometabolic risk factors and their management in association with CVD events in women vs men with type 1 diabetes enrolled in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study. DESIGN, SETTING, AND PARTICIPANTS This cohort study used data obtained during the combined DCCT (randomized clinical trial, conducted 1983-1993) and EDIC (observational study, conducted 1994 to present) studies through April 30, 2018 (mean [SD] follow-up, 28.8 [5.8] years), at 27 clinical centers in the US and Canada. Data analyses were performed between July 2021 and April 2022. EXPOSURE During the DCCT phase, patients were randomized to intensive vs conventional diabetes therapy. MAIN OUTCOMES AND MEASURES Cardiometabolic risk factors and CVD events were assessed via detailed medical history and focused physical examinations. Blood and urine samples were assayed centrally. CVD events were adjudicated by a review committee. Linear mixed models and Cox proportional hazards models evaluated sex differences in cardiometabolic risk factors and CVD risk over follow-up. RESULTS A total of 1441 participants with type 1 diabetes (mean [SD] age at DCCT baseline, 26.8 [7.1] years; 761 [52.8%] men; 1390 [96.5%] non-Hispanic White) were included. Over the duration of the study, compared with men, women had significantly lower body mass index (BMI, calculated as weight in kilograms divided by height in meters squared; β = -0.43 [SE, 0.16]; P = .006), waist circumference (β = -10.56 cm [SE, 0.52 cm]; P < .001), blood pressure (systolic: β = -5.77 mm Hg [SE, 0.35 mm Hg]; P < .001; diastolic: β = -3.23 mm Hg [SE, 0.26 mm Hg]; P < .001), and triglyceride levels (β = -10.10 mg/dL [SE, 1.98 mg/dL]; P < .001); higher HDL cholesterol levels (β = 9.36 mg/dL [SE, 0.57 mg/dL]; P < .001); and similar LDL cholesterol levels (β = -0.76 mg/dL [SE, 1.22 mg/dL]; P = .53). Women, compared with men, achieved recommended targets more frequently for blood pressure (ie, <130/80 mm Hg: 90.0% vs 77.4%; P < .001) and triglycerides (ie, <150 mg/dL: 97.3% vs 90.5%; P < .001). However, sex-specific HDL cholesterol targets (ie, ≥50 mg/dL for women, ≥40 mg/dL for men) were achieved less often (74.3% vs 86.6%; P < .001) and cardioprotective medications were used less frequently in women than men (ie, angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker: 29.6% [95% CI, 25.7%-33.9%] vs 40.0% [95% CI, 36.1%-44.0%]; P = .001; lipid-lowering medication: 25.3% [95% CI, 22.1%-28.7%] vs 39.6% [95% CI, 36.1%-43.2%]; P < .001). Women also had significantly higher pulse rates (mean [SD], 75.2 [6.8] beats per minute vs 71.8 [6.9] beats per minute; P < .001) and hemoglobin A1c levels (mean [SD], 8.3% [1.0%] vs 8.1% [1.0%]; P = .01) and achieved targets for tighter glycemic control less often than men (ie, hemoglobin A1c <7%: 11.2% [95% CI, 9.3%-13.3%] vs 14.0% [95% CI, 12.0%-16.3%]; P = .03). CONCLUSIONS AND RELEVANCE These findings suggest that despite a more favorable cardiometabolic risk factor profile, women with type 1 diabetes did not have a significantly lower CVD event burden than men, suggesting a greater clinical impact of cardiometabolic risk factors in women vs men with diabetes. These findings call for conscientious optimization of the control of CVD risk factors in women with type 1 diabetes.
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White common bean extract remodels the gut microbiota and ameliorates type 2 diabetes and its complications: A randomized double-blinded placebo-controlled trial.
Feng, Y, Zhu, J, Wang, Q, Cao, H, He, F, Guan, Y, Li, D, Yan, J, Yang, J, Xia, Y, et al
Frontiers in endocrinology. 2022;13:999715
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Patients with type 2 diabetes (T2D) have a higher risk of macrovascular complications. Intensive glycaemic control reduces microvascular complications and exerts a modest improved effect on macrovascular outcomes. The main aim of this study was to explore the effects of white common bean extract (WCBE) on glucose metabolism and diabetic complications in patients with T2D. This study was a randomised double-blind placebo-controlled trial which enrolled ninety-six patients with T2D aged between 35 and 75 years. Participants were randomly assigned in a 1:2 ratio to the control group and WCBE group. Results showed that WCBE alleviated glucose metabolism dysbiosis and diabetic complication indices. In fact, after 2 months of an intense intervention with a WCBE treatment and in the following two-month maintenance period, the improvements to glycaemic metabolism were preserved. Furthermore, there was notable improvement of the structure of the gut microbiota, especially the enrichment of short-chain fatty acid-producing bacteria and inhibition of opportunistic pathogens. Authors conclude that WCBE may be considered as a novel prebiotic antidiabetic agent for the regulation of glucose metabolism and gut microbiota homeostasis and may slightly ameliorate diabetic complications in patients with T2D.
Abstract
OBJECTIVE Excessive carbohydrate intake is a high risk factor for increased morbidity of type 2 diabetes (T2D). A novel regimen for the dietary care of diabetes that consists of a highly active α-amylase inhibitor derived from white common bean extract (WCBE) and sufficient carbohydrates intake was applied to attenuate T2D and its complications. Furthermore, the role of gut microbiota in this remission was also investigated. METHODS We conducted a 4-month randomized double-blinded placebo-controlled trial. During the intense intervention period, ninety subjects were randomly assigned to the control group (Group C) and WCBE group (Group W). Subjects in Group C were supplemented with 1.5 g of maltodextrin as a placebo. Subjects in Group W took 1.5 g of WCBE half an hour before a meal. Fifty-five participants continued the maintenance intervention receiving the previous dietary intervention whereas less frequent follow-up. The variation in biochemical, vasculopathy and neuropathy indicators and the structure of the fecal microbiota during the intervention was analyzed. RESULT Glucose metabolism and diabetic complications showed superior remission in Group W with a 0.721 ± 0.742% decline of glycosylated hemoglobin after 4 months. The proportion of patients with diabetic peripheral neuropathy (Toronto Clinical Scoring System, TCSS ≥ 6) was significantly lower in Group W than in Group C. Both the left and right sural sensory nerve conduction velocity (SNCV-left sural and SNCV-right sural) slightly decreased in Group C and slightly increased in Group W. Additionally, the abundances of Bifidobacterium, Faecalibacterium and Anaerostipes were higher in Group W, and the abundances of Weissella, Klebsiella, Cronobacter and Enterobacteriaceae_unclassified were lower than those in Group C at month 2. At the end of month 4, Bifidobacterium remained more abundant in Group W. CONCLUSION To our knowledge, this is the first report of improvement to diabetes complications by using a dietary supplement in such a short-term period. The enrichment of SCFA-producing bacteria might be responsible for the attenuation of T2D and its complications. CLINICAL TRIAL REGISTRATION NUMBER http://www.chictr.org.cn/edit.aspx?pid=23309&htm=4, identifier ChiCTR-IOR-17013656.
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Therapeutic Effects of Butyrate on Pediatric Obesity: A Randomized Clinical Trial.
Coppola, S, Nocerino, R, Paparo, L, Bedogni, G, Calignano, A, Di Scala, C, de Giovanni di Santa Severina, AF, De Filippis, F, Ercolini, D, Berni Canani, R
JAMA network open. 2022;5(12):e2244912
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Gut microbiome (GM) could play a role in obesity. A metabolically healthy GM is maintained by a diet rich in fibre. Plant foods are fermented by the gut microbiome to produce the antiobesogenic short-chain fatty acid butyrate. The aim of this study was to evaluate whether butyrate supplementation can be effective in paediatric obesity treatment. This study was a randomised, quadruple-blind, parallel-group, placebo-controlled trial. Children were randomly assigned to the treatment group or placebo in a 1:1 ratio. Results showed that in children with obesity, oral butyrate supplementation produced a reduction of body mass index and exerted beneficial effects on glucose metabolism and inflammation. In fact, butyrate supplementation decreased homeostatic model assessment of insulin resistance [HOMA-IR] and fasting insulin levels in children with obesity. Additionally, the GM analysis supported the role of butyrate in glucose metabolism, as suggested by a more positive response in children with a higher abundance of butyrate-producing bacteria at baseline. Authors conclude that their findings support the importance of the GM-derived metabolite butyrate as a protective factor against obesity, highlighting the central role of a healthy diet and GM function to achieve an optimal endogenous production of butyrate.
Abstract
IMPORTANCE The pediatric obesity disease burden imposes the necessity of new effective strategies. OBJECTIVE To determine whether oral butyrate supplementation as an adjunct to standard care is effective in the treatment of pediatric obesity. DESIGN, SETTING, AND PARTICIPANTS A randomized, quadruple-blind, placebo-controlled trial was performed from November 1, 2020, to December 31, 2021, at the Tertiary Center for Pediatric Nutrition, Department of Translational Medical Science, University of Naples Federico II, Naples, Italy. Participants included children aged 5 to 17 years with body mass index (BMI) greater than the 95th percentile. INTERVENTIONS Standard care for pediatric obesity supplemented with oral sodium butyrate, 20 mg/kg body weight per day, or placebo for 6 months was administered. MAIN OUTCOMES AND MEASURES The main outcome was the decrease of at least 0.25 BMI SD scores at 6 months. The secondary outcomes were changes in waist circumference; fasting glucose, insulin, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, ghrelin, microRNA-221, and interleukin-6 levels; homeostatic model assessment of insulin resistance (HOMA-IR); dietary and lifestyle habits; and gut microbiome structure. Intention-to-treat analysis was conducted. RESULTS Fifty-four children with obesity (31 girls [57%], mean [SD] age, 11 [2.91] years) were randomized into the butyrate and placebo groups; 4 were lost to follow-up after receiving the intervention in the butyrate group and 2 in the placebo group. At intention-to-treat analysis (n = 54), children treated with butyrate had a higher rate of BMI decrease greater than or equal to 0.25 SD scores at 6 months (96% vs 56%, absolute benefit increase, 40%; 95% CI, 21% to 61%; P < .01). At per-protocol analysis (n = 48), the butyrate group showed the following changes as compared with the placebo group: waist circumference, -5.07 cm (95% CI, -7.68 to -2.46 cm; P < .001); insulin level, -5.41 μU/mL (95% CI, -10.49 to -0.34 μU/mL; P = .03); HOMA-IR, -1.14 (95% CI, -2.13 to -0.15; P = .02); ghrelin level, -47.89 μg/mL (95% CI, -91.80 to -3.98 μg/mL; P < .001); microRNA221 relative expression, -2.17 (95% CI, -3.35 to -0.99; P < .001); and IL-6 level, -4.81 pg/mL (95% CI, -7.74 to -1.88 pg/mL; P < .001). Similar patterns of adherence to standard care were observed in the 2 groups. Baseline gut microbiome signatures predictable of the therapeutic response were identified. Adverse effects included transient mild nausea and headache reported by 2 patients during the first month of butyrate intervention. CONCLUSIONS AND RELEVANCE Oral butyrate supplementation may be effective in the treatment of pediatric obesity. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT04620057.
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Consuming a Protein and Fiber-Based Supplement Preload Promotes Weight Loss and Alters Metabolic Markers in Overweight Adults in a 12-Week, Randomized, Double-Blind, Placebo-Controlled Trial.
Glynn, EL, Fleming, SA, Edwards, CG, Wilson, MJ, Evans, M, Leidy, HJ
The Journal of nutrition. 2022;152(6):1415-1425
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One of the challenges of reduced-calorie diets is the inability to control appetite. Reductions in food intake can lead to the activation of neurological pathways that increase hunger and food cravings. Adjusting nutrient intake has the potential to serve as an effective strategy for increasing feelings of satiety, which can lead to improved appetite control. The aim of this study was to determine if greater weight loss and greater changes in body composition and metabolic outcomes could be achieved following a 12-wk energy-restricted diet that included twice-daily consumption of a protein and fibre-based multi-ingredient nutritional supplement shake (HPF) compared with an isocaloric low-protein/lower-fibre placebo (LPF) in adults with overweight and obesity. This study is a double-blind randomised placebo-controlled study. Two hundred and six healthy adults were recruited and randomly assigned to intervention groups in a 1:1 ratio. Results show that the habitual consumption of an HPF preload 30 min before breakfast and lunch resulted in greater weight loss compared with an isocaloric LPF preload in overweight/obese adults. In addition, improved metabolic outcomes were observed in the HPF group throughout the 84-d randomized controlled trial. Authors conclude that diet composition rather than energy reduction alone may influence the success of a weight-loss regimen, potentially including protein and fibre content.
Abstract
BACKGROUND Higher protein and fiber diets promote weight management and metabolic health. OBJECTIVES This study aimed to determine if greater weight loss and positive changes in metabolic outcomes could be achieved with twice-daily consumption of a high-protein and fiber-based multi-ingredient nutritional shake (HPF) compared with an isocaloric low-protein, lower fiber-based placebo (LPF). METHODS Study procedures were conducted by an independent research organization under clinicaltrials.gov registration NCT03057873. Healthy overweight and obese adults [n = 206; BMI (kg/m2): 27-35; 70% female] were randomly assigned to HPF or LPF. All participants were prescribed an energy-restricted diet (500 kcal/d less than energy needs) and consumed a HPF (17 g protein, 6 g fiber) or LPF (1 g protein, 3 g fiber) shake 30 min before breakfast and lunch for 12 wk. Primary outcomes included body weight and total body fat percentage. Blood samples were collected at days (D) 0, 28, 56, and 84 for secondary analyses related to metabolic markers of health. RESULTS Although weight loss occurred in both groups, HPF had greater weight loss at D84 compared with LPF (-3.3 kg vs. -1.8 kg, P < 0.05). Percentage body fat decreased in both groups (HPF: -1.33%, LPF: -1.09%; P < 0.001) with no differences between groups. Serum total cholesterol, LDL cholesterol, and oxidized LDL decreased between -5.1% to -8.3%, whereas adiponectin increased over time in both groups; these changes occurred to a greater extent in HPF compared with LPF (all P < 0.05). CONCLUSIONS A multi-ingredient HPF nutritional supplement shake consumed as a preload before breakfast and lunch positively influenced weight management and metabolic outcomes in overweight adults compared with an LPF placebo. These findings suggest that specific nutrient factors (i.e., potentially including protein, fiber, and bioactive content) other than calorie reduction alone influence the success of a weight-loss regimen. This trial was registered at www.clinicaltrials.gov as NCT03057873.
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Efficacy and safety of dietary polyphenol supplementation in the treatment of non-alcoholic fatty liver disease: A systematic review and meta-analysis.
Yang, K, Chen, J, Zhang, T, Yuan, X, Ge, A, Wang, S, Xu, H, Zeng, L, Ge, J
Frontiers in immunology. 2022;13:949746
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Non-alcoholic fatty liver disease (NAFLD) is characterised by fat accumulation in the liver that can result in liver damage. NAFLD affects approximately 25% of the global population. There is evidence that dietary polyphenols can improve metabolism and insulin resistance and reduce inflammation and oxidative stress, which are the mechanisms that lead to liver damage in NAFLD. This systematic review and meta-analysis aimed to assess the effectiveness of dietary polyphenols in the treatment of non-alcoholic fatty liver disease (NAFLD). Eight dietary polyphenols, such as curcumin, resveratrol, naringenin, anthocyanin, hesperidin, catechin, silymarin, and genistein, were evaluated for their efficacy and safety. The administration of 80-3,000 mg of Curcumin for an 8-12 week duration is effective and safe for reducing body mass index, aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglycerides (TG), total cholesterol (TC), and insulin resistance (HOMA-IR). Compared with the placebo, Naringenin reduced the percentage of NAFLD grade, TG, TC, and low-density lipoprotein cholesterol and increased high-density lipoprotein cholesterol. Hesperidin may potentially decrease body mass index (BMI), AST, ALT, TG, TC, and HOMA-IR. Catechin is safe, and 500-1000 mg supplementation for 12 weeks may reduce BMI, HOMA-IR, and TG. NAFLD patients who received silymarin showed improvements in ALT and AST, as well as reductions in hepatic fat accumulation and liver stiffness. 94–2100 mg of Silymarin supplementation for 8–48 weeks may reduce liver enzyme levels. Researchers can use the results of this study to understand the clinical utility of different polyphenol supplements in the treatment of NAFLD. Because the current evidence is highly heterogeneous in nature and limited in scope, further robust research is required on various classes of polyphenols and their effectiveness in reducing the severity of NAFLD.
Abstract
Background: Dietary polyphenol treatment of non-alcoholic fatty liver disease (NAFLD) is a novel direction, and the existing clinical studies have little effective evidence for its therapeutic effect, and some studies have inconsistent results. The effectiveness of dietary polyphenols in the treatment of NAFLD is still controversial. The aim of this study was to evaluate the therapeutic efficacy of oral dietary polyphenols in patients with NAFLD. Methods: The literature (both Chinese and English) published before 30 April 2022 in PubMed, Cochrane, Medline, CNKI, and other databases on the treatment of NAFLD with dietary polyphenols was searched. Manual screening, quality assessment, and data extraction of search results were conducted strictly according to the inclusion and exclusion criteria. RevMan 5.3 software was used to perform the meta-analysis. Results: The RCTs included in this study involved dietary supplementation with eight polyphenols (curcumin, resveratrol, naringenin, anthocyanin, hesperidin, catechin, silymarin, and genistein) and 2,173 participants. This systematic review and meta-analysis found that 1) curcumin may decrease body mass index (BMI), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Triglycerides (TG) total cholesterol (TC), and Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) compared to placebo; and curcumin does not increase the occurrence of adverse events. 2) Although the meta-analysis results of all randomized controlled trials (RCTs) did not reveal significant positive changes, individual RCTs showed meaningful results. 3) Naringenin significantly decreased the percentage of NAFLD grade, TG, TC, and low-density lipoprotein cholesterol (LDL-C) and increased high-density lipoprotein cholesterol (HDL-C) but had no significant effect on AST and ALT, and it is a safe supplementation. 4) Only one team presents a protocol about anthocyanin (from Cornus mas L. fruit extract) in the treatment of NAFLD. 5) Hesperidin may decrease BMI, AST, ALT, TG, TC, HOMA-IR, and so on. 6) Catechin may decrease BMI, HOMA-IR, and TG level, and it was well tolerated by the patients. 7) Silymarin was effective in improving ALT and AST and reducing hepatic fat accumulation and liver stiffness in NAFLD patients. Conclusion: Based on current evidence, curcumin can reduce BMI, TG, TC, liver enzymes, and insulin resistance; catechin can reduce BMI, insulin resistance, and TG effectively; silymarin can reduce liver enzymes. For resveratrol, naringenin, anthocyanin, hesperidin, and catechin, more RCTs are needed to further evaluate their efficacy and safety.
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The association between environmental exposures to chlordanes, adiposity and diabetes-related features: a systematic review and meta-analysis.
Mendes, V, Ribeiro, C, Delgado, I, Peleteiro, B, Aggerbeck, M, Distel, E, Annesi-Maesano, I, Sarigiannis, D, Ramos, E
Scientific reports. 2021;11(1):14546
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Chlordane is a synthetic organochlorine pesticide used for several decades in agriculture, but also in housing for pest control. Chlordane compounds are endocrine disrupting chemicals (EDCs), which means that they may affect the natural function of hormones by blocking, mimicking, displacing, or acting to subvert their roles. The aim of this study was to investigate whether exposure to chlordane compounds increases the risk of adiposity and diabetes in humans. This study is a systematic review and meta-analysis of 31 publications. Results demonstrate that there is no association between chlordane compounds and adiposity. However, there are higher odds of having diabetes-related features with increasing levels of all the chlordane compounds evaluated. Authors conclude that an international agreement on methods to measure both exposure and outcome variables and to conduct epidemiological studies could increase the knowledge on how adverse effects of exposure to various stressors (exposome) can influence human health.
Abstract
Chlordane compounds (CHLs) are components of technical chlordane listed in the Stockholm convention on persistent organic pollutants identified as endocrine disrupting chemicals (EDCs) and may interfere with hormone biosynthesis, metabolism or action resulting in an unbalanced hormonal function. There is increasing scientific evidence showing EDCs as risk factors in the pathogenesis and development of obesity and obesity-related metabolic syndromes such as type 2 diabetes, but there is no systematized information on the effect of CHLs in humans. Our aim is to identify the epidemiological data on the association between CHLs with adiposity and diabetes using a systematic approach to identify the available data and summarizing the results through meta-analysis. We searched PubMed and Web of Science from inception up to 15 February 2021, to retrieve original data on the association between chlordanes, and adiposity or diabetes. For adiposity, regression coefficients and Pearson or Spearman correlation coefficients were extracted and converted into standardized regression coefficients. Data were combined using fixed effects meta-analyses to compute summary regression coefficients and corresponding 95% confidence intervals (95% CI). For the association between chlordanes and diabetes, Odds ratios (ORs) were extracted and the DerSimonian and Laird method was used to compute summary estimates and respective 95% CI. For both, adjusted estimates were preferred, whenever available. Among 31 eligible studies, mostly using a cross-sectional approach, the meta-analysis for adiposity was possible only for oxychlordane and transchlordane, none of them were significantly associated with adiposity [(β = 0.04, 95% CI 0.00; 0.07, I2 = 89.7%)] and (β = 0.02, 95% CI - 0.01; 0.06), respectively. For diabetes, the estimates were positive for all compounds but statistically significant for oxychlordane [OR = 1.96 (95% CI 1.19; 3.23)]; for trans-nonachlor [OR = 2.43 (95% CI 1.64; 3.62)] and for heptachlor epoxide [OR = 1.88 (95% CI 1.42; 2.49)]. Our results support that among adults, the odds of having diabetes significantly increase with increasing levels of chlordanes. The data did not allow to reach a clear conclusion regarding the association with adiposity.
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Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women.
Yoshino, M, Yoshino, J, Kayser, BD, Patti, GJ, Franczyk, MP, Mills, KF, Sindelar, M, Pietka, T, Patterson, BW, Imai, SI, et al
Science (New York, N.Y.). 2021;372(6547):1224-1229
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Nicotinamide adenine dinucleotide (NAD+) is a co-substrate for NAD+-consuming enzymes that are essential in the regulation of diverse biological processes. The aim of this study was to determine the effects of nicotinamide mononucleotide (NMN) supplementation on i) body composition, ii) skeletal muscle insulin sensitivity, and insulin signalling; and iii) muscle NAD+ content and global gene expression profile. This study is a 10-week, randomized, placebo-controlled, double-blind trial in postmenopausal women with prediabetes who were overweight or obese. Twenty-five postmenopausal women with prediabetes were randomised to the placebo group (n=12) or the NMN group (n=13). Results show that 10 weeks of NMN supplementation increases muscle insulin signalling and muscle insulin sensitivity in postmenopausal women with prediabetes who are overweight or obese. Authors conclude that the precise mechanism(s) responsible for these metabolic effects and the potential metabolic benefits of NMN supplementation in other patient populations remain to be explored.
Abstract
In rodents, obesity and aging impair nicotinamide adenine dinucleotide (NAD+) biosynthesis, which contributes to metabolic dysfunction. Nicotinamide mononucleotide (NMN) availability is a rate-limiting factor in mammalian NAD+ biosynthesis. We conducted a 10-week, randomized, placebo-controlled, double-blind trial to evaluate the effect of NMN supplementation on metabolic function in postmenopausal women with prediabetes who were overweight or obese. Insulin-stimulated glucose disposal, assessed by using the hyperinsulinemic-euglycemic clamp, and skeletal muscle insulin signaling [phosphorylation of protein kinase AKT and mechanistic target of rapamycin (mTOR)] increased after NMN supplementation but did not change after placebo treatment. NMN supplementation up-regulated the expression of platelet-derived growth factor receptor β and other genes related to muscle remodeling. These results demonstrate that NMN increases muscle insulin sensitivity, insulin signaling, and remodeling in women with prediabetes who are overweight or obese (clinicaltrial.gov NCT03151239).
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Eight-hour time-restricted feeding improves endocrine and metabolic profiles in women with anovulatory polycystic ovary syndrome.
Li, C, Xing, C, Zhang, J, Zhao, H, Shi, W, He, B
Journal of translational medicine. 2021;19(1):148
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Polycystic ovary syndrome (PCOS) is one of the most common reproductive endocrine and metabolic disorders that affects up to 10% women of childbearing age. The aim of this study was to explore the effects of time-restricted feeding (TRF) on menstruation, gonadal and metabolic parameters in women with anovulatory PCOS and propose a basis for its inclusion in the treatment of PCOS. This study is a 6-week trial with 2 consecutive periods: (1) 1-week baseline weight stabilization period; and (2) 5-week TRF period. Fifteen subjects were included in the study whose age varied between 18 and 31 years. Results show that five weeks of TRF improved menstruation, gonadal profiles, body weight, body mass index, body composition profiles, hyperinsulinemia and insulin resistance profiles, decreasing chronic inflammation markers and increasing insulin growth factor –1 [hormone]. Authors conclude that TRF may be suitable for PCOS women with appropriate counselling and patient management.
Abstract
BACKGROUND Time-restricted feeding (TRF) is a form of intermittent fasting, which is beneficial for weight loss and cardiometabolic health. Polycystic ovary syndrome (PCOS) is one of the most common reproductive endocrine and metabolic diseases affecting women of childbearing age. It is associated with an increased prevalence of metabolic syndrome, cardiovascular diseases and type 2 diabetes. The effects of TRF on PCOS patients remains undefined, here we investigated the impact of TRF on women with anovulatory PCOS. METHODS Eighteen PCOS women aged between 18 and 31 with anovulation participated in a 6-week trial which were divided into two consecutive periods: (1) 1-week baseline weight stabilization period and (2) 5-week TRF period. Fifteen participants completed the study. Changes in body weight, body mass index (BMI), Waist-to-Hip Ratio, skeletal muscle mass, body fat mass (BFM), body fat percentage (BF%), visceral fat area (VFA), luteinizing hormone (LH), follicle-stimulating hormone (FSH), LH/FSH, total testosterone (TT), sex hormone-binding globulin (SHBG), free androgen index (FAI), fasting glucose, fasting insulin (FINS), homeostasis model assessment-insulin resistance (HOMA-IR), area under the curve (AUC) for insulin (AUCIns), area under the curve (AUC) for glucose (AUCGlu), AUCIns/AUCGlu Ratio, lipids, uric acid, alanine aminotransferase (ALT), aspartate aminotransferase, high-sensitivity C-reactive protein (hsCRP), insulin-like growth factor (IGF-1), menstrual cycle and eating behaviors were evaluated. RESULTS Significant changes in body weight, BMI, BFM, BF%, VFA, TT, SHBG, FAI, FINS, HOMA-IR, AUCIns, AUCIns/AUCGlu Ratio, ALT, hsCRP and IGF-1 were found after the TRF period. An improvement in menstrual cycle irregularity was detected in 73.3% (11/15) patients. CONCLUSION The diet of TRF may be beneficial to anovulatory PCOS on weight loss especially reducing body fat, improving menstruation, hyperandrogenemia, insulin resistance and chronic inflammation. Trial registration Clinicaltrial.gov, NCT04580433, registered October 8, 2020, https://clinicaltrials.gov/ct2/show/NCT04580433.