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Nutrients Feb 2023There has been an emerging concern that non-nutritive sweeteners (NNS) can increase the risk of cardiometabolic disease. Much of the attention has focused on acute... (Meta-Analysis)
Meta-Analysis
There has been an emerging concern that non-nutritive sweeteners (NNS) can increase the risk of cardiometabolic disease. Much of the attention has focused on acute metabolic and endocrine responses to NNS. To examine whether these mechanisms are operational under real-world scenarios, we conducted a systematic review and network meta-analysis of acute trials comparing the effects of non-nutritive sweetened beverages (NNS beverages) with water and sugar-sweetened beverages (SSBs) in humans. MEDLINE, EMBASE, and The Cochrane Library were searched through to January 15, 2022. We included acute, single-exposure, randomized, and non-randomized, clinical trials in humans, regardless of health status. Three patterns of intake were examined: (1) uncoupling interventions, where NNS beverages were consumed alone without added energy or nutrients; (2) coupling interventions, where NNS beverages were consumed together with added energy and nutrients as carbohydrates; and (3) delayed coupling interventions, where NNS beverages were consumed as a preload prior to added energy and nutrients as carbohydrates. The primary outcome was a 2 h incremental area under the curve (iAUC) for blood glucose concentration. Secondary outcomes included 2 h iAUC for insulin, glucagon-like peptide 1 (GLP-1), gastric inhibitory polypeptide (GIP), peptide YY (PYY), ghrelin, leptin, and glucagon concentrations. Network meta-analysis and confidence in the network meta-analysis (CINeMA) were conducted in R-studio and CINeMA, respectively. Thirty-six trials involving 472 predominantly healthy participants were included. Trials examined a variety of single NNS (acesulfame potassium, aspartame, cyclamate, saccharin, stevia, and sucralose) and NNS blends (acesulfame potassium + aspartame, acesulfame potassium + sucralose, acesulfame potassium + aspartame + cyclamate, and acesulfame potassium + aspartame + sucralose), along with matched water/unsweetened controls and SSBs sweetened with various caloric sugars (glucose, sucrose, and fructose). In uncoupling interventions, NNS beverages (single or blends) had no effect on postprandial glucose, insulin, GLP-1, GIP, PYY, ghrelin, and glucagon responses similar to water controls (generally, low to moderate confidence), whereas SSBs sweetened with caloric sugars (glucose and sucrose) increased postprandial glucose, insulin, GLP-1, and GIP responses with no differences in postprandial ghrelin and glucagon responses (generally, low to moderate confidence). In coupling and delayed coupling interventions, NNS beverages had no postprandial glucose and endocrine effects similar to controls (generally, low to moderate confidence). The available evidence suggests that NNS beverages sweetened with single or blends of NNS have no acute metabolic and endocrine effects, similar to water. These findings provide support for NNS beverages as an alternative replacement strategy for SSBs in the acute postprandial setting.
Topics: Humans; Sugar-Sweetened Beverages; Aspartame; Ghrelin; Glucagon; Cyclamates; Network Meta-Analysis; Blood Glucose; Glucose; Non-Nutritive Sweeteners; Beverages; Sucrose; Insulin; Sugars; Glucagon-Like Peptide 1; Water
PubMed: 36839408
DOI: 10.3390/nu15041050 -
Obesity (Silver Spring, Md.) Jun 2020The objective of this study was to evaluate the effect of skipping breakfast on body composition and cardiometabolic risk factors. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The objective of this study was to evaluate the effect of skipping breakfast on body composition and cardiometabolic risk factors.
METHODS
This study conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating breakfast skipping compared with breakfast consumption. Inclusion criteria included age ≥ 18, intervention duration ≥ 4 weeks, ≥ 7 participants per group, and ≥ 1 body composition measure. Random-effects meta-analyses of the effect of breakfast skipping on body composition and cardiometabolic risk factors were performed.
RESULTS
Seven RCTs (n = 425 participants) with an average duration of 8.6 weeks were included. Compared with breakfast consumption, breakfast skipping significantly reduced body weight (weighted mean difference [WMD] = -0.54 kg [95% CI: -1.05 to -0.03], P = 0.04, I = 21.4%). Percent body fat was reported in 5 studies and was not significantly different between breakfast skippers and consumers. Three studies reported on low-density lipoprotein cholesterol (LDL), which was increased in breakfast skippers as compared with breakfast consumers (WMD = 9.24 mg/dL [95% CI: 2.18 to 16.30], P = 0.01). Breakfast skipping did not lead to significant differences in blood pressure, total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, C-reactive protein, insulin, fasting glucose, leptin, homeostatic model assessment of insulin resistance, or ghrelin.
CONCLUSIONS
Breakfast skipping may have a modest impact on weight loss and may increase LDL in the short term. Further studies are needed to provide additional insight into the effects of breakfast skipping.
Topics: Adolescent; Adult; Aged; Body Composition; Breakfast; Cardiovascular Diseases; Female; Humans; Middle Aged; Randomized Controlled Trials as Topic; Risk Factors; Young Adult
PubMed: 32304359
DOI: 10.1002/oby.22791 -
Neuroscience and Biobehavioral Reviews Sep 2017The brain-gut-axis is an interdependent system affecting neural functions and controlling our eating behaviour. In recent decades, neuroimaging techniques have... (Review)
Review
The brain-gut-axis is an interdependent system affecting neural functions and controlling our eating behaviour. In recent decades, neuroimaging techniques have facilitated its investigation. We systematically looked into functional and neurochemical brain imaging studies investigating how key molecules such as ghrelin, glucagon-like peptide-1 (GLP-1), peptide tyrosine-tyrosine (PYY), cholecystokinin (CCK), leptin, glucose and insulin influence the function of brain regions regulating appetite and satiety. Of the 349 studies published before July 2016 identified in the database search, 40 were included (27 on healthy and 13 on obese subjects). Our systematic review suggests that the plasma level of ghrelin, the gut hormone promoting appetite, is positively correlated with activation in the pre-frontal cortex (PFC), amygdala and insula and negatively correlated with activation in subcortical areas such as the hypothalamus. In contrast, the plasma levels of glucose, insulin, leptin, PYY, GLP-1 affect the same brain regions conversely. Our study integrates previous investigations of the gut-brain matrix during food-intake and homeostatic regulation and may be of use for future meta-analyses of brain-gut interactions.
Topics: Appetite; Brain; Gastrointestinal Tract; Hormones; Humans; Satiation
PubMed: 28669754
DOI: 10.1016/j.neubiorev.2017.06.013 -
Journal of Sport and Health Science Mar 2023This study investigates the effects of exercise training on exerkines in patients with type 2 diabetes mellitus to determine the optimal exercise prescription. (Meta-Analysis)
Meta-Analysis Review
Exercise training-induced changes in exerkine concentrations may be relevant to the metabolic control of type 2 diabetes mellitus patients: A systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
This study investigates the effects of exercise training on exerkines in patients with type 2 diabetes mellitus to determine the optimal exercise prescription.
METHODS
A systematic search for relevant studies was performed in 3 databases. Randomized controlled trials investigating the effects of exercise training on at least one of the following exerkines were included: adiponectin, apelin, brain-derived neurotrophic factor, fetuin-A, fibroblast growth factor-21, follistatin, ghrelin, interleukin (IL)-6, IL-8, IL-10, IL-15, IL-18, leptin, myostatin, omentin, resistin, retinol-binding protein 4, tumor necrosis factor-α, and visfatin.
RESULTS
Forty randomized controlled trials were selected for data extraction (n = 2160). Exercise training induces changes in adiponectin, fetuin-A, fibroblast growth factor-21, IL-6, IL-10, leptin, resistin, and tumor necrosis factor-α levels but has no significant effects on apelin, IL-18, and ghrelin compared to controls. Physical exercise training favored large and positive changes in pooled exerkines (i.e., an overall effect size calculated from several exerkines) (Hedge's g = 1.02, 95% confidence interval (95%CI): 0.76-1.28), which in turn were related to changes in glycated hemoglobin (mean difference (MD) = -0.81%, 95%CI: -0.95% to -0.67%), fasting glucose (MD = -23.43 mg/dL, 95%CI: -30.07 mg/dL to -16.80 mg/dL), waist circumference (MD = -3.04 cm, 95%CI: -4.02 cm to -2.07 cm), and body mass (MD = -1.93 kg, 95%CI: -2.00 kg to -1.86 kg). Slightly stronger effects were observed with aerobic, resistance, or high-intensity interval protocols at moderate- to vigorous-intensity and with programs longer than 24 weeks that comprise at least 3 sessions per week and more than 60 min per session.
CONCLUSION
Exercise training represents an anti-inflammatory therapy and metabolism-improving strategy with minimal side effects for patients with type 2 diabetes mellitus.
Topics: Humans; Diabetes Mellitus, Type 2; Resistin; Apelin; Leptin; Ghrelin; Interleukin-10; Interleukin-18; Adiponectin; alpha-2-HS-Glycoprotein; Tumor Necrosis Factor-alpha; Randomized Controlled Trials as Topic; Exercise; Fibroblast Growth Factors
PubMed: 36351545
DOI: 10.1016/j.jshs.2022.11.003 -
Advances in Nutrition (Bethesda, Md.) Sep 2023Ghrelin is an orexigenic hormone primarily released by the stomach and has 2 isoforms: acylated ghrelin (AG) and de-acylated ghrelin (DAG), that appear to have different... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ghrelin is an orexigenic hormone primarily released by the stomach and has 2 isoforms: acylated ghrelin (AG) and de-acylated ghrelin (DAG), that appear to have different functions in humans.
OBJECTIVES
To perform a systematic review and meta-analysis of the association between plasma concentrations of total ghrelin (TG), AG, and DAG and perceptions of hunger in healthy adults.
METHODS
The following criteria were used for inclusion: 1) sample contained adults ≥18 y of age, 2) body mass index [BMI kg/m] was ≥18.5, 3) ghrelin was sampled through blood, 4) subjective hunger was measured on a validated scale, 5) study reported a Pearson product correlation of ghrelin or had relevant figure(s) for data extraction, 6) participants were healthy with no overt disease, 7) protocols contained no physical activity or weight loss medication that suppressed appetite, 8) interventions were conducted without environmental manipulations. Moderators assessed were age, BMI, percentage of body fat (%BF), macronutrient content of test meals, energy intake (kcals), sex, and ghrelin isoform (AG, DAG, or TG).
RESULTS
The analysis included 47 studies (110 trials, n = 1799, age: 31.4 ± 12.0 y, BMI: 26.0 ± 4.75 kg/m) and measured AG (n = 47 trials), DAG (n = 12 trials), and TG (n = 51 trials). The overall model indicated that ghrelin concentrations and perceptions of hunger were moderately correlated (r = 0.43, P < 0.001), and ghrelin isoform significantly moderated this relationship (AG: r = 0.60, P < 0.001; TG: r = 0.215, P = 0.01; DAG: r = 0.53, P = 0.695). Other significant moderators included age (b = -0.02, P = 0.01), BMI (b = -0.03, P = 0.05), %BF (b = -0.03, P = 0.05), energy intake (b = 0.0003, P = 0.04), and percentage of carbohydrates of test meals (b = 0.008, P = 0.05).
CONCLUSIONS
Ghrelin is associated with perceptions of hunger in humans, and this relationship is strengthened when AG is isolated; thus, AG may have a large impact on hunger signals in various populations. Future research should attempt to understand the role of DAG in hunger sensations.
Topics: Adult; Humans; Young Adult; Child, Preschool; Hunger; Ghrelin; Energy Intake; Body Mass Index; Perception; Appetite
PubMed: 37536563
DOI: 10.1016/j.advnut.2023.07.011 -
Nutrients Feb 2021Ghrelin is an orexigenic hormone which favors food-seeking behavior and has been postulated to be a biomarker of stress. We conducted a systematic review and... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Ghrelin is an orexigenic hormone which favors food-seeking behavior and has been postulated to be a biomarker of stress. We conducted a systematic review and meta-analysis on the evolution of ghrelin levels following acute stress.
METHODS
The PubMed, Cochrane Library, Embase, and ScienceDirect databases were searched for studies reporting ghrelin levels before and after acute stress in humans.
RESULTS
We included ten studies for a total of 348 patients. Acute stress (intervention) was always in a laboratory. Acute stress was psychological (Trier Social Stress Test), physical, or mixed (cold pressure test). The overall meta-analysis demonstrated an increase in ghrelin after the stress intervention (ES = 0.21, 95CI 0.09 to 0.34) compared with baseline levels. Stratification by time demonstrated an acute increase in ghrelin levels in the five minutes immediately following the initiation of stress (0.29, 0.10 to 0.48) but without any difference after. Obese individuals had a more significant (ES = 0.51, 95CI 0.18 to 0.84) and prolonged increase in ghrelin levels for up to 45 min compared with non-obese individuals who had a significant increase only five minutes after stress. Moreover, the ghrelin levels increased in response to stress with BMI (coefficient 0.028, 0.01 to 0.49; = 0.013) and decreased with the time after the stress intervention (coefficient -0.007, -0.014 to -0.001; = 0.025).
CONCLUSION
Ghrelin is a biomarker of stress, with a short-term increase following acute stress. Obese individuals have both a higher and prolonged response, emphasizing the link between obesity and stress.
Topics: Biomarkers; Ghrelin; Humans; Stress, Physiological; Stress, Psychological
PubMed: 33673594
DOI: 10.3390/nu13030784 -
Endocrine-related Cancer Sep 2016Ghrelin is a hormone with multiple physiologic functions, including promotion of growth hormone release, stimulation of appetite and regulation of energy homeostasis.... (Review)
Review
Ghrelin is a hormone with multiple physiologic functions, including promotion of growth hormone release, stimulation of appetite and regulation of energy homeostasis. Treatment with ghrelin/ghrelin-receptor agonists is a prospective therapy for disease-related cachexia and malnutrition. In vitro studies have shown high expression of ghrelin in cancer tissue, although its role including its impact in cancer risk and progression has not been established. We performed a systematic literature review to identify peer-reviewed human or animal in vivo original research studies of ghrelin, ghrelin-receptor agonists, or ghrelin genetic variants and the risk, presence, or growth of cancer using structured searches in PubMed database as well as secondary searches of article reference lists, additional reviews and meta-analyses. Overall, 45 (73.8%) of the 61 studies reviewed, including all 11 involving exogenous ghrelin/ghrelin-receptor agonist treatment, reported either a null (no statistically significant difference) or inverse association of ghrelin/ghrelin-receptor agonists or ghrelin genetic variants with cancer risk, presence or growth; 10 (16.7%) studies reported positive associations; and 6 (10.0%) reported both negative or null and positive associations. Differences in serum ghrelin levels in cancer cases vs controls (typically lower) were reported for some but not all cancers. The majority of in vivo studies showed a null or inverse association of ghrelin with risk and progression of most cancers, suggesting that ghrelin/ghrelin-receptor agonist treatment may have a favorable safety profile to use for cancer cachexia. Additional large-scale prospective clinical trials as well as basic bioscientific research are warranted to further evaluate the safety and benefits of ghrelin treatment in patients with cancer.
Topics: Animals; Ghrelin; Humans; Neoplasms; Receptors, Ghrelin
PubMed: 27552970
DOI: 10.1530/ERC-16-0130 -
Sports Medicine (Auckland, N.Z.) Nov 2021Ghrelin is a peptide hormone predominantly produced by the stomach. It exerts a wide range of functions including stimulating growth hormone release and regulating...
BACKGROUND
Ghrelin is a peptide hormone predominantly produced by the stomach. It exerts a wide range of functions including stimulating growth hormone release and regulating appetite, food intake, and glucose and lipid metabolism. Since physical exercise affects all these aspects, a particular interest is accorded to the relationship between ghrelin and exercise. This systematic review aimed to summarize the current available data on the topic for a better understanding of the relationship.
METHODS
An extensive computerized search was performed in the PubMed and SPORTDiscus databases for retrieving relevant articles. The search contained the following keywords: ghrelin, appetite-related peptides, gastrointestinal peptides, gastrointestinal hormones, exercise, acute exercise, chronic exercise, training, and physical activity. Studies investigating the effects of acute/chronic exercise on circulating forms of ghrelin were included.
RESULTS
The initial search identified 840 articles. After screening, 80 articles were included. Despite a heterogeneity of studies and a variability of the findings, the review suggests that acute exercise suppresses acyl ghrelin production regardless of the participants and the exercise characteristics. Long- and very long-term exercise training programs mostly resulted in increased total and des-acyl ghrelin production. The increase is more noticeable in overweight/obese individuals, and is most likely due to weight loss resulting from the training program.
CONCLUSION
The review suggests that exercise may impact ghrelin production. While the precise mechanisms are unclear, the effects are likely due to blood flow redistribution and weight loss for acute and chronic exercise, respectively. These changes are expected to be metabolically beneficial. Further research is needed for a better understanding of the relationship between ghrelin and exercise.
Topics: Appetite; Exercise; Ghrelin; Humans; Obesity; Weight Loss
PubMed: 34374968
DOI: 10.1007/s40279-021-01518-6 -
Frontiers in Endocrinology 2023Circulating adipokines and ghrelin affect bone remodeling by regulating the activation and differentiation of osteoblasts and osteoclasts. Although the correlation... (Meta-Analysis)
Meta-Analysis
CONTEXT
Circulating adipokines and ghrelin affect bone remodeling by regulating the activation and differentiation of osteoblasts and osteoclasts. Although the correlation between adipokines, ghrelin, and bone mineral density (BMD) has been studied over the decades, its correlations are still controversial. Accordingly, an updated meta-analysis with new findings is needed.
OBJECTIVE
This study aimed to explore the impact of serum adipokine and ghrelin levels on BMD and osteoporotic fractures through a meta-analysis.
DATA SOURCES
Studies published till October 2020 in Medline, Embase, and the Cochrane Library were reviewed.
STUDY SELECTION
We included studies that measured at least one serum adipokine level and BMD or fracture risk in healthy individuals. We excluded studies with one or more of the following: patients less than 18 years old, patients with comorbidities, who had undergone metabolic treatment, obese patients, patients with high physical activities, and a study that did not distinguish sex or menopausal status.
DATA EXTRACTION
We extracted the data that include the correlation coefficient between adipokines (leptin, adiponectin, and resistin) and ghrelin and BMD, fracture risk by osteoporotic status from eligible studies.
DATA SYNTHESIS
A meta-analysis of the pooled correlations between adipokines and BMD was performed, demonstrating that the correlation between leptin and BMD was prominent in postmenopausal women. In most cases, adiponectin levels were inversely correlated with BMD. A meta-analysis was conducted by pooling the mean differences in adipokine levels according to the osteoporotic status. In postmenopausal women, significantly lower leptin (SMD = -0.88) and higher adiponectin (SMD = 0.94) levels were seen in the osteoporosis group than in the control group. By predicting fracture risk, higher leptin levels were associated with lower fracture risk (HR = 0.68), whereas higher adiponectin levels were associated with an increased fracture risk in men (HR = 1.94) and incident vertebral fracture in postmenopausal women (HR = 1.18).
CONCLUSIONS
Serum adipokines levels can utilize to predict osteoporotic status and fracture risk of patients.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021224855, identifier CRD42021224855.
Topics: Male; Humans; Female; Adolescent; Bone Density; Leptin; Adipokines; Adiponectin; Ghrelin; Osteoporotic Fractures
PubMed: 37181034
DOI: 10.3389/fendo.2023.1044039 -
Journal of Cachexia, Sarcopenia and... Apr 2022Cancer cachexia is an unmet clinical need that affects more than 50% of patients with cancer. The systemic inflammatory response, which is mediated by a network of... (Review)
Review
Cancer cachexia is an unmet clinical need that affects more than 50% of patients with cancer. The systemic inflammatory response, which is mediated by a network of cytokines, has an established role in the genesis and maintenance of cancer as well as in cachexia; yet, the specific role of the cytokine milieu in cachexia requires elucidation. This systematic review aims to examine the relationship between cytokines and the cachexia syndrome in patients with incurable cancer. The databases MEDLINE, EMBASE, CINAHL, CENTRAL, PsycINFO, and Web of Science were searched for studies published between 01/01/2004 and 06/01/2020. Included studies measured cytokines and their relationship with cachexia and related symptoms/signs in adults with incurable cancer. After title screening (n = 5202), the abstracts (n = 1264) and the full-text studies (n = 322) were reviewed independently by two authors. The quality assessment of the selected papers was conducted using the modified Downs and Black checklist. Overall, 1277 patients with incurable cancer and 155 healthy controls were analysed in the 17 eligible studies. The mean age of the patients was 64 ± 15 (mean ± standard deviation). Only 34% of included participants were female. The included studies were assessed as moderate-quality to high-quality evidence (mean quality score: 7.8; range: 5-10). A total of 31 cytokines were examined in this review, of which interleukin-6 (IL-6, 14 studies) and tumour necrosis factor-α (TNF-α, 12 studies) were the most common. The definitions of cachexia and the weight-loss thresholds were highly variable across studies. Although the data could not be meta-analysed due to the high degree of methodological heterogeneity, the findings were discussed in a systematic manner. IL-6, TNF-α, and IL-8 were greater in cachectic patients compared with healthy individuals. Also, IL-6 levels were higher in cachectic participants as opposed to non-cachectic patients. Leptin, interferon-γ, IL-1β, IL-10, adiponectin, and ghrelin did not demonstrate any significant difference between groups when individuals with cancer cachexia were compared against non-cachectic patients or healthy participants. These findings suggest that a network of cytokines, commonly IL-6, TNF-α, and IL-8, are associated with the development of cachexia. Yet, this relationship is not proven to be causative and future studies should opt for longitudinal designs with consistent methodological approaches, as well as adequate techniques for analysing and reporting the results.
Topics: Aged; Cachexia; Cytokines; Female; Humans; Interleukin-6; Male; Middle Aged; Neoplasms; Tumor Necrosis Factor-alpha
PubMed: 35080147
DOI: 10.1002/jcsm.12912