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Neurology and Therapy Apr 2023Fenfluramine (FFA) is an amphetamine derivative that promotes the release and blocks the neuronal reuptake of serotonin. Initially introduced as an appetite suppressant,...
INTRODUCTION
Fenfluramine (FFA) is an amphetamine derivative that promotes the release and blocks the neuronal reuptake of serotonin. Initially introduced as an appetite suppressant, FFA also showed antiseizure properties. This systematic review aimed to assess the efficacy and safety of FFA for the treatment of seizures in patients with epilepsy.
METHODS
We systematically searched (in week 3 of June 2022) MEDLINE, the Cochrane Central Register of Controlled Trials, and the US National Institutes of Health Clinical Trials Registry. Randomized, double- or single-blinded, placebo-controlled studies of FFA in patients with epilepsy and uncontrolled seizures were identified. Efficacy outcomes included the proportions of patients with ≥ 50% and 100% reductions in baseline seizure frequency during the treatment period. Tolerability outcomes included the proportions of patients who withdrew from treatment for any reason and suffered adverse events (AEs). The risk of bias in the included studies was assessed according to the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions. The risk ratio (RR) along with the 95% confidence interval (CI) were estimated for each outcome.
RESULTS
Three trials were identified and a total of 469 Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) subjects were randomized. All three trials were judged to be at low risk of biases. In patients with DS, the RRs for ≥ 50% and 100% reductions in convulsive seizure frequency for the FFA group compared to placebo were 5.61 (95% CI 2.73-11.54) and 4.71 (95% CI 0.57-39.30), respectively. In patients with LGS, the corresponding RRs for ≥ 50% and 100% reductions in drop seizure frequency were 2.58 (95% CI 1.33-5.02) and 0.50 (95% CI 0.031-7.81), respectively. The drug was withdrawn for any reason in 10.1% and 5.8% of patients receiving FFA and placebo, respectively (RR 1.79, 95% CI 0.89-3.59). Treatment discontinuation due to AEs occurred in 5.4% and 1.2% of FFA- and placebo-treated patients, respectively (RR 3.63, 95% CI 0.93-14.16). Decreased appetite, diarrhoea, fatigue, and weight loss were AEs associated with FFA treatment.
CONCLUSION
Fenfluramine reduces the frequency of seizures in patients with DS and LGS. Decreased appetite, diarrhoea, fatigue, and weight loss are non-cardiovascular AEs associated with FFA.
PubMed: 36853503
DOI: 10.1007/s40120-023-00452-1 -
Nutrients Sep 2021The primary aim was to systematically review the current evidence investigating if dietary interventions rich in protein lead to improved body weight management in... (Meta-Analysis)
Meta-Analysis
Are Dietary Proteins the Key to Successful Body Weight Management? A Systematic Review and Meta-Analysis of Studies Assessing Body Weight Outcomes after Interventions with Increased Dietary Protein.
The primary aim was to systematically review the current evidence investigating if dietary interventions rich in protein lead to improved body weight management in adults with excessive body weight. The secondary aim was to investigate potential modifying effects of phenotyping. A systematic literature search in PubMed, Web of Science, and Cochrane Library identified 375 randomized controlled trials with 43 unique trials meeting the inclusion criteria. The Cochrane collaboration tool was used for a thorough risk of bias assessment. Based on 37 studies evaluating effects of dietary protein on body weight, the participants with increased protein intake (ranging from 18-59 energy percentage [E%]) were found to reduce body weight by 1.6 (1.2; 2.0) kg (mean [95% confidence interval]) compared to controls (isocaloric interventions with energy reduction introduced in certain studies). Individuals with prediabetes were found to benefit more from a diet high in protein compared to individuals with normoglycemia, as did individuals without the obesity risk allele (AA genotype) compared to individuals with the obesity risk alleles (AG and GG genotypes). Thus, diets rich in protein would seem to have a moderate beneficial effect on body weight management.
Topics: Adult; Body Mass Index; Body Weight; Diet, High-Protein; Dietary Proteins; Exercise; Female; Humans; Male; Middle Aged; Obesity; Overweight; Randomized Controlled Trials as Topic; Weight Gain; Weight Loss; Young Adult
PubMed: 34579069
DOI: 10.3390/nu13093193 -
European Review For Medical and... Sep 2021We aimed this systematic review to analyze and review the currently available published literature related to long COVID, understanding its pattern, and predicting the...
We aimed this systematic review to analyze and review the currently available published literature related to long COVID, understanding its pattern, and predicting the long-term effects on survivors. We thoroughly searched the databases for relevant articles till May 2021. The research articles that met our inclusion and exclusion criteria were assessed and reviewed by two independent researchers. After preliminary screening of the identified articles through title and abstract, 249 were selected. Consequently, 167 full-text articles were assessed and reviewed based on our inclusion criteria and thus 20 articles were regarded as eligible and analyzed in the present analysis. All the studies included adult population aged between 18 and above 60 years. The median length of hospital stay of the COVID-19 patients during the acute infection phase ranged from 8 days to 17 days. The most common prevalent long-term symptoms in COVID-19 patients included persistent fatigue and dyspnea in almost all of the studies. Other reported common symptoms included: shortness of breath, cough, joint pain, chest pain or tightness, headache, loss of smell/taste, sore throat, diarrhea, loss of memory, depression, anxiety. Associated cardiovascular events included arrhythmias, palpitations and hypotension, increased HR, venous thromboembolic diseases, myocarditis, and acute/decompensated heart failure as well. Among neurological manifestations headache, peripheral neuropathy symptoms, memory issues, concentration, and sleep disorders were most commonly observed with varying frequencies. Mental health issues affecting mental abilities, mood fluctuations namely anxiety and depression, and sleep disorders were commonly seen. Further, diarrhea, vomiting, digestive disorders, and Loss of appetite or weight loss are common gastrointestinal manifestations. Therefore, appropriate clinical evaluation is required in long COVID cases which in turn may help us to identify the risk factors, etiology, and to my help, we treat them early with appropriate management strategies.
Topics: COVID-19; Humans; SARS-CoV-2; Post-Acute COVID-19 Syndrome
PubMed: 34533807
DOI: 10.26355/eurrev_202109_26669 -
The Cochrane Database of Systematic... Sep 2022Chronic loss of appetite in cystic fibrosis concerns both individuals and families. Appetite stimulants have been used to help cystic fibrosis patients with chronic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic loss of appetite in cystic fibrosis concerns both individuals and families. Appetite stimulants have been used to help cystic fibrosis patients with chronic anorexia attain optimal body mass index (BMI) and nutritional status. However, these may have adverse effects on clinical status. This is an updated version of the original review.
OBJECTIVES
To systematically search for and evaluate the evidence on the beneficial effects of appetite stimulants in the management of cystic fibrosis-related anorexia and synthesise reports of any side effects.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Cystic Fibrosis Trials Register and online trials registries; handsearched reference lists; and contacted local and international experts to identify relevant trials. Last search of the Cystic Fibrosis Trials Register: 23 May 2022. Last search of online trial registries: 10 May 2022.
SELECTION CRITERIA
Randomised and quasi-randomised controlled trials of appetite stimulants compared to placebo, control, no treatment or different appetite stimulants, or to the same appetite stimulants at different doses or regimens for at least one month in adults and children with cystic fibrosis.
DATA COLLECTION AND ANALYSIS
Review authors independently extracted data and assessed risk of bias of the included trials. We used the GRADE approach to assess the certainty of the evidence and performed meta-analyses.
MAIN RESULTS
We included four trials (70 participants) comparing appetite stimulants (cyproheptadine hydrochloride and megestrol acetate) to placebo; the numbers of adults or children within each trial were not always reported. We assessed the certainty of evidence as low due to the small number of participants, incomplete or selective outcome reporting, and unclear risk of selection bias. Regarding our primary outcomes, a meta-analysis of two trials (42 participants) showed that appetite stimulants may produce a larger increase in weight (kg) at three months (mean difference (MD) 1.25 kg, 95% confidence interval (Cl) 0.45 to 2.05), and one trial (17 participants) showed a similar result at six months (MD 3.80 kg, 95% CI 1.27 to 6.33) (both low-certainty evidence). Results also showed that weight z score may increase with appetite stimulants compared to placebo at three months (MD 0.61, 95% CI 0.29 to 0.93; 3 studies; 40 participants; P < 0.001) and at six months (MD 0.74, 95% CI 0.26 to 1.22; 1 trial; 17 participants). There was no evidence of a difference in effect between cyproheptadine hydrochloride and megestrol acetate for either outcome. Only one trial (25 participants) reported analysable data for body composition (BMI), with results favouring cyproheptadine hydrochloride compared to placebo; a further trial (16 participants) narratively agreed with this result. All four trials reported on lung function at durations ranging from two to nine months. Considering analysable data, two trials (42 participants) found that appetite stimulants may make little or no difference in forced expiratory volume at one second (FEV) % predicted at three months, and one trial (17 participants) found similar results at six months. Two further three-month trials narratively agreed with these results. Limited information was reported for secondary outcomes. Two trials (23 participants) reported results showing that appetite stimulants may increase appetite compared to placebo at three months (odds ratio 45.25, 95% CI 3.57 to 573.33; low-certainty evidence). Only one study reported on quality of life, finding that cyproheptadine reduced fatigue in two participants compared with none with placebo. One study (25 participants) found no difference in energy intake between appetite stimulant or placebo at three months. Insufficient reporting of adverse effects prevented a full determination of their impact. Two studies (33 participants) narratively reported similar requirements for additional antibiotics between appetite stimulants and placebo at three months. AUTHORS' CONCLUSIONS: At six months in adults and children, appetite stimulants improved only two of the outcomes of this review: weight (or weight z score) and subjectively reported appetite. Insufficient reporting of side effects prevented a full determination of their impact. Whilst the data may suggest the potential use of appetite stimulants in treating anorexia in adults and children with cystic fibrosis, this is based upon low-certainty evidence from a small number of trials, therefore firm conclusions cannot be drawn. Clinicians need to be aware of the potential adverse effects of appetite stimulants and actively monitor any individuals prescribed these medications accordingly. Research is required to determine meaningful surrogate measures for appetite and to define what constitutes quality weight gain. Future trials of appetite stimulants should use a validated measure of symptoms including a disease-specific instrument for measuring poor appetite. This review highlights the need for multicentred, adequately powered, and well-designed trials to evaluate agents to safely increase appetite in people with cystic fibrosis and to establish the optimal mode of treatment.
Topics: Adult; Anorexia; Anti-Bacterial Agents; Appetite Stimulants; Child; Cyproheptadine; Cystic Fibrosis; Humans; Megestrol Acetate; Quality of Life
PubMed: 36149378
DOI: 10.1002/14651858.CD008190.pub3 -
International Journal of Molecular... Apr 2023Appetite dysregulation is one of the factors contributing to anorexia, bulimia nervosa, obesity, and diabetes. Essential oils or fragrant compounds have been proven to... (Review)
Review
Appetite dysregulation is one of the factors contributing to anorexia, bulimia nervosa, obesity, and diabetes. Essential oils or fragrant compounds have been proven to regulate food intake and energy expenditure; hence, this study aimed to summarize their effects on appetite and the underlying mechanisms. The PubMed and Web of Science databases were searched until July 2022. Only two of the 41 studies were performed clinically, and the remaining 39 used animal models. Oral administration was the most common route, and a dosage range of 100-2000 mg/kg for mice or 2-32 mg/kg for rats was applied, with a duration of 12 days to 4 weeks, followed by inhalation (10-10 mg/cage or 10-10 mg/cm within 1 h). Approximately 11 essential oil samples and 22 fragrant compounds were found to increase appetite, while 12 essential oils and seven compounds decreased appetite. These fragrant components can exert appetite-regulating effects via leptin resistance, the activity of sympathetic/parasympathetic nerves, or the mRNA expression of neuropeptide Y (NPY)/agouti-related protein (AgRP), cocaine- and amphetamine-regulated transcript (CART)/proopiomelanocortin (POMC) in the hypothalamus. Fragrance memory and cognitive processes may also play roles in appetite regulation. The findings of this study accentuate the potential of essential oils and fragrant compounds to regulate appetite and eating disorders.
Topics: Rats; Mice; Animals; Appetite; Oils, Volatile; Nerve Tissue Proteins; Neuropeptide Y; Hypothalamus; Leptin; Appetite Regulation; Agouti-Related Protein; Eating
PubMed: 37175666
DOI: 10.3390/ijms24097962 -
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 -
Frontiers in Neuroendocrinology Oct 2022Impaired hormonal regulation of appetite may contribute to higher cardiovascular risk in bipolar disorder (BD). We performed a systematic review and meta-analysis of... (Meta-Analysis)
Meta-Analysis Review
Impaired hormonal regulation of appetite may contribute to higher cardiovascular risk in bipolar disorder (BD). We performed a systematic review and meta-analysis of studies investigating peripheral blood levels of appetite-regulating hormones in BD and controls. A total of 32 studies were included. Leptin and insulin levels were significantly elevated in patients with BD during euthymia, but not in other mood states. Greater differences in the number of male participants between patients with BD and healthy controls were associated with higher effect size estimates for the levels of insulin. There were significant positive correlations of effect size estimates for the levels of adiponectin with the percentage of individuals with type I BD and duration of BD. Our findings point to the mechanisms underlying high rates of cardiometabolic comorbidities in BD. Moreover, they suggest that investigating hormonal regulation of appetite might help to understand differences in the neurobiology of BD types.
Topics: Humans; Male; Bipolar Disorder; Appetite; Adiponectin; Insulin
PubMed: 35792198
DOI: 10.1016/j.yfrne.2022.101013 -
Avicenna Journal of Phytomedicine 2023Cinnamon is extracted from the inner bark of Cinnamomum trees. Recent studies have indicated that cinnamon is a safe and cost-effective treatment for improving body... (Review)
Review
OBJECTIVE
Cinnamon is extracted from the inner bark of Cinnamomum trees. Recent studies have indicated that cinnamon is a safe and cost-effective treatment for improving body weight, lipid profiles, insulin resistance, and blood pressure. This systematic review aimed to summarize the effect of cinnamon supplementation on adipokines and appetite-regulating hormones
MATERIALS AND METHODS
This comprehensive literature search was conducted using databases such as PubMed, Scopus, ISI Web of Science, and Google Scholar up to March 2022 without any limitation. The quality of eligible studies was evaluated through the Cochrane Collaboration's tool for assessing the risk of bias
RESULTS
This systematic review included six clinical trial studies (363 participants), among which, only one study was performed on children, and two investigations were conducted on obese participants. A decreasing effect was found in the level of leptin and visfatin after cinnamon supplementation. Two out of three studies examined adiponectin levels and revealed non-significant effects of cinnamon consumption on this parameter. Two studies evaluated ghrelin levels and found an increase after cinnamon supplementation. The result of cinnamon supplementation on other biomarkers such as glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1, and resistin was inconsistent.
CONCLUSION
The result of this systematic review indicated the increasing effect of cinnamon supplementation on ghrelin levels and decreasing effect on leptin and visfatin levels. However, more clinical data are required to clarify the beneficial effects of cinnamon on adipokines levels due to the controversial findings of the studies.
PubMed: 38089418
DOI: 10.22038/AJP.2022.21538 -
Paediatric Drugs Jul 2022There are numerous potential factors that may affect growth in children with epilepsy, and these must be evaluated in any child with appetite and weight concerns.... (Review)
Review
There are numerous potential factors that may affect growth in children with epilepsy, and these must be evaluated in any child with appetite and weight concerns. Antiseizure medications (ASMs) have potential adverse effects, and many may affect appetite, thus impacting normal growth and weight gain. The aim of this review is to focus on the impact of both epilepsy and ASMs on appetite and weight in children. We systematically reviewed studies using Medline assessing the impact of ASMs on appetite and weight in children. Eligible studies included randomized controlled trials and open-label studies (open-label extension and interventional) that targeted or included the pediatric population (0-18 years of age). Each study was classified using the American Academy of Neurology (AAN) Classification of Evidence for Therapeutic Studies, and the level of evidence for impact on appetite and weight in children was graded. ASMs associated with decreased appetite and/or weight loss include fenfluramine, topiramate, zonisamide, felbamate, rufinamide, stiripentol, cannabidiol, brivaracetam and ethosuximide; ASMs with minimal impact on weight and appetite in children include oxcarbazepine, eslicarbazepine, lamotrigine, levetiracetam, lacosamide, carbamazepine, vigabatrin and clobazam. The ASM most robustly associated with increased appetite and/or weight gain is valproic acid; however, both pregabalin and perampanel may also lead to modest weight gain or increased appetite in children. Certain ASMs may impact both appetite and weight, which may lead to increased morbidity of the underlying disease and impaired adherence to the treatment regimen.
Topics: Anticonvulsants; Appetite; Child; Epilepsy; Humans; Lamotrigine; Weight Gain
PubMed: 35596110
DOI: 10.1007/s40272-022-00505-2 -
Nutrients Jun 2023Anorexia of aging is a common problem in older adults. Depending on the setting, its prevalence varies from about 10% (among community-dwelling older adults) to over 30%... (Review)
Review
Anorexia of aging is a common problem in older adults. Depending on the setting, its prevalence varies from about 10% (among community-dwelling older adults) to over 30% in acute wards and nursing homes. The objective of this systematic review was to establish the prevalence of poor appetite in frail persons ≥60 years of age. We performed a literature search for studies where the prevalence of anorexia of aging among frail and pre-frail old adults was reported. 957 articles on this topic were identified. After eligibility assessment, three articles were included in the review. The studies included 4657 community-dwelling older adults. The weighted total prevalence of anorexia of aging in all the included studies was 11.3%. Among frail and pre-frail participants, loss of appetite was reported in 20.5% (weighted estimate). Overall, robust status was associated with a 63% lower probability of concomitant anorexia of ageing (OR 0.37, 95%CI 0.21-0.65, = 0.0005). Frailty or risk of frailty are associated with more prevalent anorexia of ageing. This has potential practical implications; however, more research, especially to elucidate the direction of the relation, is needed.
Topics: Humans; Aged; Aged, 80 and over; Frailty; Frail Elderly; Anorexia; Appetite; Aging; Geriatric Assessment
PubMed: 37447292
DOI: 10.3390/nu15132966