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Advances in Nutrition (Bethesda, Md.) Feb 2024Choline is essential for proper liver, muscle, brain, lipid metabolism, cellular membrane composition, and repair. Understanding genetic determinants of circulating... (Review)
Review
The Relationship of Circulating Choline and Choline-Related Metabolite Levels with Health Outcomes: A Scoping Review of Genome-Wide Association Studies and Mendelian Randomization Studies.
Choline is essential for proper liver, muscle, brain, lipid metabolism, cellular membrane composition, and repair. Understanding genetic determinants of circulating choline metabolites can help identify new determinants of choline metabolism, requirements, and their link to disease endpoints. We conducted a scoping review to identify studies assessing the association of genetic polymorphisms on circulating choline and choline-related metabolite concentrations and subsequent associations with health outcomes. This study follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement scoping review extension. Literature was searched to September 28, 2022, in 4 databases: Embase, MEDLINE, Web of Science, and the Biological Science Index. Studies of any duration in humans were considered. Any genome-wide association study (GWAS) investigating genetic variant associations with circulating choline and/or choline-related metabolites and any Mendelian randomization (MR) study investigating the association of genetically predicted circulating choline and/or choline-related metabolites with any health outcome were considered. Qualitative evidence is presented in summary tables. From 1248 total reviewed articles, 53 were included (GWAS = 27; MR = 26). Forty-two circulating choline-related metabolites were tested in association with genetic variants in GWAS studies, primarily trimethylamine N-oxide, betaine, sphingomyelins, lysophosphatidylcholines, and phosphatidylcholines. MR studies investigated associations between 52 total unique choline metabolites and 66 unique health outcomes. Of these, 47 significant associations were reported between 16 metabolites (primarily choline, lysophosphatidylcholines, phosphatidylcholines, betaine, and sphingomyelins) and 27 health outcomes including cancer, cardiovascular, metabolic, bone, and brain-related outcomes. Some articles reported significant associations between multiple choline types and the same health outcome. Genetically predicted circulating choline and choline-related metabolite concentrations are associated with a wide variety of health outcomes. Further research is needed to assess how genetic variability influences choline metabolism and whether individuals with lower genetically predicted circulating choline and choline-related metabolite concentrations would benefit from a dietary intervention or supplementation.
Topics: Humans; Choline; Betaine; Genome-Wide Association Study; Sphingomyelins; Mendelian Randomization Analysis; Lysophosphatidylcholines; Phosphatidylcholines; Polymorphism, Single Nucleotide
PubMed: 38128611
DOI: 10.1016/j.advnut.2023.100164 -
Current Medical Research and Opinion Nov 2013Allergic rhinitis is a complex inflammatory disease whose pathophysiology involves local and systemic mechanisms. Rupatadine, a molecule with intense antihistaminic... (Review)
Review
BACKGROUND
Allergic rhinitis is a complex inflammatory disease whose pathophysiology involves local and systemic mechanisms. Rupatadine, a molecule with intense antihistaminic activity and with antagonist PAF effects through its interaction with specific receptors, is indicated for the treatment of intermittent or persistent allergic rhinitis and urticaria.
SCOPE
This systematic review was aimed at identifying in the most important databases, up to January 2013, the double-blind placebo-controlled randomized trials administering rupatadine in allergic rhinitis. No restriction was introduced for treatment duration and dose, study design, population age, allergen exposition and disease classification. The methodological quality of included studies and risk of bias were systematically assessed. Meta-analysis was performed when possible to summarize information.
FINDINGS
Seventeen of 413 initially identified records were fully assessed for eligibility. Ten trials involving 2573 patients overall met the inclusion criteria and entered the analysis. Their internal validity was satisfactory. Data synthesis showed that rupatadine is superior to placebo in relieving the overall allergy symptoms on reflective (SMD: -0.37, 95% CI -0.46 to -0.27; p < 0.00001) and instantaneous (SMD: -0.41, 95% CI -0.71 to -0.11; p = 0.007) assessment, the nasal symptoms considered together (reflective SMD: -0.36, 95% CI -0.48 to -0.25; p < 0.00001; instantaneous SMD: -0.39, 95% CI -0.61 to -0.17; p = 0.0004) or individually and ocular symptoms. Inter-study heterogeneity was low for the main outcomes and the risk of publication bias was judged as unlikely. A number of secondary endpoints were favorably affected by rupatadine. No difference was observed in the incidence of total adverse reactions between rupatadine and placebo (OR 1.23, 95% CI 0.95 to 1.59; p = 0.12).
CONCLUSION
Randomized double-blind controlled trials show a favorable risk-benefit ratio in rupatadine for the treatment of allergic rhino-conjunctivitis. This evidence is strengthened when data are pooled in the form of meta-analysis, where accurate and robust effect estimations are derived from a large population.
Topics: Conjunctivitis, Allergic; Cyproheptadine; Histamine Antagonists; Humans; Platelet Activating Factor; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Treatment Outcome; Urticaria
PubMed: 23826741
DOI: 10.1185/03007995.2013.822855 -
Brain Injury Jul 2008There has been increasing interest in the role of cholinomimetic agents in the long-term management of cognitive impairment following traumatic brain injury. This paper... (Review)
Review
PRIMARY OBJECTIVE
There has been increasing interest in the role of cholinomimetic agents in the long-term management of cognitive impairment following traumatic brain injury. This paper aims to assess the evidence accumulated thus far.
METHODS
Studies are identified by searching MEDLINE, EMBASE and PsychINFO, contacting experts and pharmaceutical companies and hand searching bibliographies. All study designs are included.
MAIN OUTCOME AND RESULTS
This study identified 25 papers that studied cholinesterase inhibitors, physostigmine and choline in mild-to-severe traumatic brain injury. The outcome with cholinesterase inhibitors and choline is suggestive but not conclusive while physostigmine appears of little benefit. A lack of rigorous studies and a plethora of outcome measures preclude drawing definitive conclusions. Further randomized controlled trials are urgently required.
Topics: Brain Injuries; Cholinesterase Inhibitors; Cognition Disorders; Cytidine Diphosphate Choline; Humans; Lecithins; Neuropsychological Tests; Nootropic Agents; Physostigmine; Surface-Active Agents; Time Factors
PubMed: 18568705
DOI: 10.1080/02699050802132495 -
Journal of Alzheimer's Disease : JAD 2023Choline alphoscerate (alpha glyceryl phosphorylcholine, α-GPC) is a choline-containing phospholipid used as a medicine or nutraceutical to improve cognitive function... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Choline alphoscerate (alpha glyceryl phosphorylcholine, α-GPC) is a choline-containing phospholipid used as a medicine or nutraceutical to improve cognitive function impairment occurring in neurological conditions including adult-onset dementia disorders. Despite its 1985 marketing authorization, there are still discrepancies between countries regarding its approval as a prescription medicine and discussions about its effectiveness.
OBJECTIVE
This study aimed to evaluate the efficacy of the α-GPC compound for treating cognitive impairment in patients with adult-onset neurological disorders.
METHODS
Relevant studies were identified by searching PubMed, Web of Science, and Embase. Studies that evaluated the effects of α-GPC alone or in combination with other compounds on adult-onset cognitive impairment reporting cognition, function, and behavior were considered. We assessed the risk of bias of selected studies using the Cochrane risk of bias tool.
RESULTS
A total of 1,326 studies and 300 full-text articles were screened. We included seven randomized controlled trials (RCTs) and one prospective cohort study that met our eligibility criteria. We found significant effects of α-GPC in combination with donepezil on cognition [4 RCTs, mean difference (MD):1.72, 95% confidence interval (CI): 0.20 to 3.25], functional outcomes [3 RCTs, MD:0.79, 95% CI: 0.34 to 1.23], and behavioral outcomes [4 RCTs; MD: -7.61, 95% CI: -10.31 to -4.91]. We also observed that patients who received α-GPC had significantly better cognition than those who received either placebo or other medications [MD: 3.50, 95% CI: 0.36 to 6.63].
CONCLUSION
α-GPC alone or in combination with donepezil improved cognition, behavior, and functional outcomes among patients with neurological conditions associated with cerebrovascular injury.
Topics: Humans; Donepezil; Glycerylphosphorylcholine; Cognitive Dysfunction; Cognition Disorders; Cognition; Randomized Controlled Trials as Topic
PubMed: 36683513
DOI: 10.3233/JAD-221189 -
International Journal of Molecular... Nov 2017The multifunctional sphingosine-1-phosphate (S1P) is a lipid signaling molecule and central regulator in the development of several cancer types. In recent years,... (Review)
Review
The multifunctional sphingosine-1-phosphate (S1P) is a lipid signaling molecule and central regulator in the development of several cancer types. In recent years, intriguing information has become available regarding the role of S1P in the progression of Glioblastoma multiforme (GBM), the most aggressive and common brain tumor in adults. S1P modulates numerous cellular processes in GBM, such as oncogenesis, proliferation and survival, invasion, migration, metastasis and stem cell behavior. These processes are regulated via a family of five G-protein-coupled S1P receptors (S1PR1-5) and may involve mainly unknown intracellular targets. Distinct expression patterns and multiple intracellular signaling pathways of each S1PR subtype enable S1P to exert its pleiotropic cellular actions. Several studies have demonstrated alterations in S1P levels, the involvement of S1PRs and S1P metabolizing enzymes in GBM pathophysiology. While the tumorigenic actions of S1P involve the activation of several kinases and transcription factors, the specific G-protein (Gi, Gq, and G12/13)-coupled signaling pathways and downstream mediated effects in GBM remain to be elucidated in detail. This review summarizes the recent findings concerning the role of S1P and its receptors in GBM. We further highlight the current insights into the signaling pathways considered fundamental for regulating the cellular processes in GMB and ultimately patient prognosis.
Topics: Adult; Brain Neoplasms; Cell Movement; Disease Progression; GTP-Binding Proteins; Glioblastoma; Humans; Lysophospholipids; Neoplasm Invasiveness; Neoplasm Metastasis; Prognosis; Receptors, Lysosphingolipid; Sphingosine
PubMed: 29149079
DOI: 10.3390/ijms18112448 -
Neonatology 2012Lung lavage with diluted surfactant has emerged as an innovative treatment for meconium aspiration syndrome (MAS). However, the treatment effect has not yet been fully... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Lung lavage with diluted surfactant has emerged as an innovative treatment for meconium aspiration syndrome (MAS). However, the treatment effect has not yet been fully established.
OBJECTIVE
To investigate the effects of surfactant lavage therapy for MAS by a systematic meta-analysis.
METHODS
Relevant studies were identified by database searches in MEDLINE (from 1950), EMBASE (from 1980), and CENTRAL, up to June 2010, and by additional hand searches. Meta-analyses were separately conducted for randomized controlled trials (RCTs) and non-randomized controlled studies (NRSs). Risk of bias was assessed and clinical as well as statistical heterogeneities were also investigated in explaining the potential bias.
RESULTS
Two RCTs (87 patients) and eight NRSs (178 patients) were identified. From the results of the meta-analysis of RCTs, surfactant lavage significantly decreased death or the need for extracorporeal membrane oxygenation (RR 0.34, 95% CI 0.11, 0.99). An interventional benefit was indicated for other outcomes, although it was not statistically significant based only on the two RCTs. Results from the analysis of outcomes from NRSs are consistent with those from RCTs and demonstrated a beneficial effect, which could be considered as supporting evidence.
CONCLUSIONS
Lung lavage with diluted surfactant appeared to improve the clinical outcome in infants with MAS. Given that less than 100 infants were included in the two RCTs, the findings of this study may still be regarded as insufficient evidence. Further research will be needed to confirm the benefit as well as to refine the lavage technique.
Topics: Biological Products; Bronchoalveolar Lavage; Drug Combinations; Fatty Alcohols; Humans; Infant, Newborn; Meconium Aspiration Syndrome; Phosphatidylglycerols; Proteins; Pulmonary Surfactants; Randomized Controlled Trials as Topic; Survival Rate; Treatment Outcome
PubMed: 22067375
DOI: 10.1159/000329822 -
The Cochrane Database of Systematic... 2000People with Alzheimer's disease have been found to have a relative lack of the enzyme responsible for converting choline into acetylcholine within the brain. Lecithin is... (Review)
Review
BACKGROUND
People with Alzheimer's disease have been found to have a relative lack of the enzyme responsible for converting choline into acetylcholine within the brain. Lecithin is a major dietary source of choline, so extra consumption may assist in the production of acetylcholine and reduce some of the symptoms of dementia.
OBJECTIVES
To determine the efficacy of lecithin in the treatment of dementia or cognitive impairment.
SEARCH STRATEGY
The Cochrane Dementia and Cognitive Impairment Group Register of Clinical Trials has been searched, as have the electronic databases MEDLINE, EMBASE, Psychlit, ISI and Current Contents. Reference lists and relevant books have been examined.
SELECTION CRITERIA
All unconfounded, randomised trials comparing lecithin with placebo in a treatment period longer than one day, in patients with dementia of the Alzheimer type, vascular dementia, mixed vascular and Alzheimer's disease, unclassified or other dementia or unclassified cognitive impairment not fulfilling the criteria for dementia are eligible for inclusion.
DATA COLLECTION AND ANALYSIS
Data are extracted by two independent reviewers and cross checked. Meta-analyses are performed when more than one trial provide data on a comparable outcome on sufficiently similar patients. Random effects analyses are performed whenever heterogeneity between results appears to be present. Standardised mean difference are used due do the use of different scales and periods of treatment. Odds ratios for dichotomous data are pooled using the Mantel-Haenszel or DerSimonian and Laird methods.
MAIN RESULTS
Eleven randomised trials have been identified involving patients with Alzheimer's disease (265 patients) and Parkinsonian dementia (21 patients). No trials reported any clear clinical benefit of lecithin. Few trials contributed data to meta-analyses. The only statistically significant result was in favour of placebo for adverse events, based on one trial, which appears likely to be a spurious result.
REVIEWER'S CONCLUSIONS
Evidence from randomised trials does not support the use of lecithin in the treatment of patients with dementia or cognitive impairment. A moderate effect cannot be ruled out, but results from the small trials to date do not indicate priority for a large randomised trial.
Topics: Alzheimer Disease; Cognition Disorders; Dementia; Humans; Phosphatidylcholines
PubMed: 10796586
DOI: 10.1002/14651858.CD001015 -
The Cochrane Database of Systematic... 2003Alzheimer's disease sufferers have been found to have a lack of the enzyme responsible for converting choline into acetylcholine within the brain. Lecithin is a major... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Alzheimer's disease sufferers have been found to have a lack of the enzyme responsible for converting choline into acetylcholine within the brain. Lecithin is a major dietary source of choline, so extra consumption may reduce the progression of dementia.
OBJECTIVES
To determine the efficacy of lecithin in the treatment of dementia or cognitive impairment.
SEARCH STRATEGY
The Cochrane Dementia and Cognitive Improvement Group's Specialized Register was searched on 15 May 2002 using the terms lecithin and phosphaditylcholine. This contains records from all major databases and many trials databases. Reference lists and relevant books have been examined.
SELECTION CRITERIA
All unconfounded, randomized trials comparing lecithin with placebo in a treatment period longer than one day, in patients with dementia of the Alzheimer type, vascular dementia, mixed vascular and Alzheimer's disease, unclassified or other dementia or unclassified cognitive impairment not fulfilling the criteria for dementia are eligible for inclusion.
DATA COLLECTION AND ANALYSIS
Data were extracted by two independent reviewers and cross-checked. Meta-analyses were performed when more than one trial provided data on a comparable outcome on sufficiently similar patients. Random effects analyses were performed whenever heterogeneity between results appeared to be present. Standardised differences in mean outcome measures were used due do the use of different scales and periods of treatment. Odds ratios for dichotomous data were pooled using the Mantel-Haenszel or DerSimonian and Laird methods.
MAIN RESULTS
Twelve randomized trials have been identified involving patients with Alzheimer's disease (265 patients), Parkinsonian dementia (21 patients) and subjective memory problems (90 patients). No trials reported any clear clinical benefit of lecithin for Alzheimer's disease or Parkinsonian dementia. Few trials contributed data to meta-analyses. The only statistically significant result was in favour of placebo for adverse events, based on one trial, which appears likely to be a spurious result. A dramatic result in favour of lecithin was obtained in a trial of subjects with subjective memory problems.
REVIEWER'S CONCLUSIONS
Evidence from randomized trials does not support the use of lecithin in the treatment of patients with dementia. A moderate effect cannot be ruled out, but results from the small trials to date do not indicate priority for a large randomized trial.
Topics: Alzheimer Disease; Cognition Disorders; Dementia; Humans; Phosphatidylcholines; Randomized Controlled Trials as Topic
PubMed: 12917896
DOI: 10.1002/14651858.CD001015 -
European Journal of Obstetrics,... Jun 2017Accurate and early identification of women at risk from alcohol consumption during pregnancy allows education and support programmes to be targeted at those most in... (Review)
Review
Accurate and early identification of women at risk from alcohol consumption during pregnancy allows education and support programmes to be targeted at those most in need. We aimed to conduct a systematic review to compare the efficacy of blood analysis and maternal self-report in detecting at risk women during pregnancy. This review investigated diagnostic accuracy. We searched four databases (Medline, Embase, Psychinfo and CINAHL) for relevant articles and conducted hand searches of recent issues of key journals in the field. No restriction was placed on inclusion in terms of publication date or language. Studies were deemed eligible if they were original research and included a direct comparison of the results of blood biomarker analysis and self-reported alcohol use for the detection of alcohol consumption in pregnant women. Quality appraisal of included studies was conducted using the QUADAS II tool. Eight studies met the inclusion criteria. Gamma-glutamyltransferase (GGT) was investigated in five studies, mean corpuscular volume (MCV) and phosphatidylethanol (PEth) in three studies and carbohydrate deficient transferrin (CDT), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and whole blood associated acetaldehyde assay (WBAA) were each investigated in two studies. Although all of the studies were rated of good methodological quality, none of the biomarkers had both high sensitivity and specificity when compared to self-report. There was some evidence that a combination of biomarkers, or combining biomarkers with self-report, increases accuracy. In summary, the blood biomarkers examined were of limited use in screening for low and moderate alcohol consumption in pregnancy when compared to self-report. However, certain biomarkers, such and CDT and PEth may complement self-report and help improve the accuracy of diagnosis.
Topics: Alanine Transaminase; Alcohol Drinking; Aspartate Aminotransferases; Biomarkers; Erythrocyte Indices; Female; Glycerophospholipids; Humans; MEDLINE; Pregnancy; Self Report; Sensitivity and Specificity; Transferrin; gamma-Glutamyltransferase
PubMed: 28426943
DOI: 10.1016/j.ejogrb.2017.04.005 -
The Cochrane Database of Systematic... 2000Alzheimer's disease sufferers have been found to have a lack of the enzyme responsible for converting choline into acetylcholine within the brain. Lecithin is a major... (Review)
Review
BACKGROUND
Alzheimer's disease sufferers have been found to have a lack of the enzyme responsible for converting choline into acetylcholine within the brain. Lecithin is a major dietary source of choline, so extra consumption may reduce the progression of dementia.
OBJECTIVES
To determine the efficacy of lecithin in the treatment of dementia or cognitive impairment.
SEARCH STRATEGY
The Cochrane Dementia and Cognitive Impairment Group Register of Clinical Trials has been searched, as have the electronic databases MEDLINE, EMBASE, Psychlit, ISI and Current Contents. Reference lists and relevant books have been examined.
SELECTION CRITERIA
All unconfounded, randomized trials comparing lecithin with placebo in a treatment period longer than one day, in patients with dementia of the Alzheimer type, vascular dementia, mixed vascular and Alzheimer's disease, unclassified or other dementia or unclassified cognitive impairment not fulfilling the criteria for dementia are eligible for inclusion.
DATA COLLECTION AND ANALYSIS
Data were extracted by two independent reviewers and cross-checked. Meta-analyses were performed when more than one trial provided data on a comparable outcome on sufficiently similar patients. Random effects analyses were performed whenever heterogeneity between results appeared to be present. Standardised mean difference were used due do the use of different scales and periods of treatment. Odds ratios for dichotomous data were pooled using the Mantel-Haenszel or DerSimonian and Laird methods.
MAIN RESULTS
Twelve randomized trials have been identified involving patients with Alzheimer's disease (265 patients), Parkinsonian dementia (21 patients) and subjective memory problems (90 patients). No trials reported any clear clinical benefit of lecithin for Alzheimer's disease or Parkinsonian dementia. Few trials contributed data to meta-analyses. The only statistically significant result was in favour of placebo for adverse events, based on one trial, which appears likely to be a spurious result. A dramatic result in favour of lecithin was obtained in a trial of subjects with subjective memory problems.
REVIEWER'S CONCLUSIONS
Evidence from randomized trials does not support the use of lecithin in the treatment of patients with dementia. A moderate effect cannot be ruled out, but results from the small trials to date do not indicate priority for a large randomized trial.
Topics: Alzheimer Disease; Cognition Disorders; Dementia; Humans; Phosphatidylcholines; Randomized Controlled Trials as Topic
PubMed: 11034695
DOI: 10.1002/14651858.CD001015