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PloS One 2024To systematically evaluate the safety and efficacy of antioxidant therapy in children and adolescents with attention deficit hyperactivity disorder (ADHD). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To systematically evaluate the safety and efficacy of antioxidant therapy in children and adolescents with attention deficit hyperactivity disorder (ADHD).
METHODS
Randomized controlled trials and prospective studies on antioxidant therapy in children and adolescents with ADHD were searched in PubMed, Embase, and Cochrane Library from the inception of databases to November 12, 2022. Two investigators independently screened the literature, extracted data, and evaluated the quality of the included studies. Network meta-analysis (PROSPERO registration number CRD 42023382824) was carried out by using R Studio 4.2.1.
RESULTS
48 studies involving 12 antioxidant drugs (resveratrol, pycnogenol, omega-3, omega-6, quercetin, phosphatidylserine, almond, vitamin D, zinc, folic acid, ginkgo biloba, Acetyl-L-carnitine) were finally included, with 3,650 patients. Network meta-analysis showed that omega-6 (0.18), vitamin D (0.19), and quercetin (0.24) were the top three safest drugs according to SUCRA. The omega-3 (SUCRA 0.35), pycnogenol (SUCRA 0.36), and vitamin D (SUCRA 0.27) were the most effective in improving attention, hyperactivity, and total score of Conners' parent rating scale (CPRS), respectively. In terms of improving attention, hyperactivity, and total score of Conners' teacher rating scale (CTRS), pycnogenol (SUCRA 0.32), phosphatidylserine+omega-3 (SUCRA 0.26), and zinc (SUCRA 0.34) were the most effective, respectively. In terms of improving attention, hyperactivity and total score of ADHD Rating Scale-Parent, the optimal agents were phosphatidylserine (SUCRA 0.39), resveratrol+MPH (SUCRA 0.24), and phosphatidylserine (SUCRA 0.34), respectively. In terms of improving attention, hyperactivity and total score of ADHD Rating Scale-Teacher, pycnogenol (SUCRA 0.32), vitamin D (SUCRA 0.31) and vitamin D (SUCRA 0.18) were the optimal agents, respectively. The response rate of omega-3+6 was the highest in CGI (SUCRA 0.95) and CPT (SUCRA 0.42).
CONCLUSION
The rankings of safety and efficacy of the 12 antioxidants vary. Due to the low methodological quality of the included studies, the probability ranking cannot fully explain the clinical efficacy, and the results need to be interpreted with caution. More high-quality studies are still needed to verify our findings.
Topics: Child; Humans; Adolescent; Attention Deficit Disorder with Hyperactivity; Antioxidants; Network Meta-Analysis; Resveratrol; Quercetin; Prospective Studies; Phosphatidylserines; Fatty Acids, Omega-3; Vitamin D; Zinc
PubMed: 38547138
DOI: 10.1371/journal.pone.0296926 -
Nanomaterials (Basel, Switzerland) May 2023Liposomes have been used for several decades for the encapsulation of drugs and bioactives in cosmetics and cosmeceuticals. On the other hand, the use of these... (Review)
Review
Liposomes have been used for several decades for the encapsulation of drugs and bioactives in cosmetics and cosmeceuticals. On the other hand, the use of these phospholipid vesicles in food applications is more recent and is increasing significantly in the last ten years. Although in different stages of technological maturity-in the case of cosmetics, many products are on the market-processes to obtain liposomes suitable for the encapsulation and delivery of bioactives are highly expensive, especially those aiming at scaling up. Among the bioactives proposed for cosmetics and food applications, vitamins are the most frequently used. Despite the differences between the administration routes (oral for food and mainly dermal for cosmetics), some challenges are very similar (e.g., stability, bioactive load, average size, increase in drug bioaccessibility and bioavailability). In the present work, a systematic review of the technological advancements in the nanoencapsulation of vitamins using liposomes and related processes was performed; challenges and future perspectives were also discussed in order to underline the advantages of these drug-loaded biocompatible nanocarriers for cosmetics and food applications.
PubMed: 37177102
DOI: 10.3390/nano13091557 -
Frontiers in Aging Neuroscience 2023Many lines of evidence suggest that mitochondria have a central role in aging-related neurodegenerative diseases, such as Alzheimer's disease (AD). Mitochondrial...
Many lines of evidence suggest that mitochondria have a central role in aging-related neurodegenerative diseases, such as Alzheimer's disease (AD). Mitochondrial dysfunction, cerebral energy dysmetabolism and oxidative damage increase with age, and are early event in AD pathophysiology and may precede amyloid beta (Aβ) plaques. probes of mitochondrial function and energy metabolism are therefore crucial to characterize the bioenergetic abnormalities underlying AD risk, and their relationship to pathophysiology and cognition. A majority of the research conducted in humans have used F-fluoro-deoxygluose (FDG) PET to image cerebral glucose metabolism (CMRglc), but key information regarding oxidative phosphorylation (OXPHOS), the process which generates 90% of the energy for the brain, cannot be assessed with this method. Thus, there is a crucial need for imaging tools to measure mitochondrial processes and OXPHOS in the human brain. Phosphorus-magnetic resonance spectroscopy (P-MRS) is a non-invasive method which allows for the measurement of OXPHOS-related high-energy phosphates (HEP), including phosphocreatine (PCr), adenosine triphosphate (ATP), and inorganic phosphate (Pi), in addition to potential of hydrogen (pH), as well as components of phospholipid metabolism, such as phosphomonoesters (PMEs) and phosphodiesters (PDEs). Herein, we provide a systematic review of the existing literature utilizing the P-MRS methodology during the normal aging process and in patients with mild cognitive impairment (MCI) and AD, with an additional focus on individuals at risk for AD. We discuss the strengths and limitations of the technique, in addition to considering future directions toward validating the use of P-MRS measures as biomarkers for the early detection of AD.
PubMed: 37273652
DOI: 10.3389/fnagi.2023.1183228 -
Cureus Dec 2020Alzheimer's disease (AD) is caused by several risk factors leading to dementia. It's diagnosis usually depends on clinical presentation and certain biomarkers in the... (Review)
Review
Alzheimer's disease (AD) is caused by several risk factors leading to dementia. It's diagnosis usually depends on clinical presentation and certain biomarkers in the cerebrospinal fluid (CSF). The brain has a high content of cholesterol and the metabolism of cholesterol in the brain can be associated with beta-amyloid plaques formation, which is seen in Alzheimer's disease. Given these implications, we studied if plasma lipid levels can vary in Alzheimer's disease and if these can be used as biomarkers to diagnose and predict the progression of Alzheimer's disease. Certain mutations in the brain cholesterol transport receptors and proteins and their association with Alzheimer's were also studied. This systematic review abides by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched multiple databases, such as Pubmed, Google Scholar, Pubmed central, ScienceDirect, Web of Science, and Medline with the help of keywords like Alzheimer's disease, cognitive impairment, plasma lipid biomarkers, cholesterol, brain cholesterol metabolism separately and in combination with each other. We collected 49 quality appraised articles on the association between plasma lipids and Alzheimer's disease and the genetic mutations in alleles related to cholesterol metabolism and Alzheimer's disease by applying the inclusion and exclusion criteria. Based on the finding of the studies reviewed, we found an association between plasma lipids, polymorphisms in genes associated with cholesterol transport, and Alzheimer's disease. Increased serum low-density lipoprotein (LDL-C), triglycerides (TG), total cholesterol (TC), sphingolipids, 24S hydroxycholesterol (24S-HC), 27O hydroxycholesterol (27O-HC) was associated with Alzheimer's. Decreased high-density lipoprotein (HDL-C) and phospholipids were noticed. Genetic mutations in apolipoprotein E (ApoE), apolipoprotein B (ApoB), apolipoprotein A (ApoA), ATP binding cassette transporter 1 (ABCA1), ATP binding cassette transporter 7 (ABCA7), amyloid precursor protein (APP), cytochrome P450 family 46 subfamilies A member 1 (CYP46A1), presenilin 1 (PSEN1), presenilin 2 (PSEN2) are also associated with increased risk of Alzheimer's disease. This study found an association between plasma lipids and Alzheimer's, proving that plasma lipids can be used as biomarkers for early diagnosis of Alzheimer's disease. It may also help predict the prognosis and stage the disease severity. Further studies are needed to find out the exact mechanism behind these changes.
PubMed: 33457117
DOI: 10.7759/cureus.12008 -
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 -
Journal of Dairy Science Jan 2023Dairy consumption is inversely related to the risk of developing type 2 diabetes in epidemiological research. One proposed hypothesis is that phospholipid (PL) species... (Review)
Review
Graduate Student Literature Review: A scoping review on the impact of consumption of dairy products on phosphatidylcholine and lysophosphatidylcholine in circulation and the liver in human studies and animal models.
Dairy consumption is inversely related to the risk of developing type 2 diabetes in epidemiological research. One proposed hypothesis is that phospholipid (PL) species associated with dairy consumption mediate this relationship. This scoping review aimed to identify the existing literature in animal and human trials investigating the impact of dairy products, including milk, yogurt, and cheese as well as dairy-derived PL supplementation on PL and its species in the circulation, summarizing the characteristics of these studies and identifying research gaps. A systematic search was conducted across 3 databases (PubMed, Scopus, and Web of Science) in March 2021. Of 2,427 identified references, 15 studies (7 humans and 8 animal studies) met the eligibility criteria and were included in the final narrative synthesis. The evidence base was heterogeneous, involving a variety of clinical and preclinical studies, metabolically healthy or obese/diabetic participants or animal models, and displayed mixed findings. Circulating postprandial concentrations of total PL were elevated acutely but unchanged after longer intervention with dairy products. The PL concentration remained stable even after a high dosage of milk supplemented with dairy-derived PL, which may be related to increased fecal excretion; however, certain phosphatidylcholine (PC) or lysophosphatidylcholine species were increased in circulation by interventions. These include several PC species with 32 to 38 total carbons in addition to the dairy biomarkers C15:0 and C17:0. The results of this scoping review demonstrate a small body of literature indicating that dairy products can influence blood concentrations of PC and lysophosphatidylcholine species in both rodents and humans without alteration of total PL and PC. There is a lack of well-designed trials in humans and animals that explore the potential differences between individual dairy foods on PL species. In addition, trials to understand the bioactive properties of PC and lysophosphatidylcholine species on cardiometabolic risk are needed.
Topics: Animals; Humans; Dairy Products; Diabetes Mellitus, Type 2; Diet; Liver; Lysophosphatidylcholines; Milk; Models, Animal; Phosphatidylcholines; Students; Yogurt
PubMed: 36400621
DOI: 10.3168/jds.2022-21938 -
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 -
International Journal of Molecular... Dec 2022Aim: The single-nucleotide polymorphism (SNP) rs713041, located in the regulatory region, is required to incorporate selenium into the selenoprotein glutathione... (Meta-Analysis)
Meta-Analysis Review
Aim: The single-nucleotide polymorphism (SNP) rs713041, located in the regulatory region, is required to incorporate selenium into the selenoprotein glutathione peroxidase 4 (GPX4) and has been found to have functional consequences. This systematic review aimed to conduct a meta-analysis to determine whether there is an association between GPX4 (rs713041) SNP and the risk of diseases in humans and its correlation with selenium status. Material and methods: A systematic search for English-language manuscripts published between January 1990 and November 2022 was carried out using six databases: CINAHL, Cochrane, Medline, PubMed, Scopus and Web of Science. Odds ratios (ORs) and 95% confidence intervals (CIs) were applied to assess a relationship between GPX4 (rs713041) SNP and the risk of different diseases based on three genetic models. Review Manager 5.4 and Comprehensive Meta-Analysis 4 software were used to perform the meta-analysis and carry out Egger’s test for publication bias. Results: Data from 21 articles were included in the systematic review. Diseases were clustered according to the physiological system affected to understand better the role of GPX4 (rs713041) SNP in developing different diseases. Carriers of the GPX4 (rs173041) T allele were associated with an increased risk of developing colorectal cancer in additive and dominant models (p = 0.02 and p = 0.004, respectively). In addition, carriers of the T allele were associated with an increased risk of developing stroke and hypertension in the additive, dominant and recessive models (p = 0.002, p = 0.004 and p = 0.01, respectively). On the other hand, the GPX4 (rs713041) T allele was associated with a decreased risk of developing pre-eclampsia in the additive, dominant and recessive models (p < 0.0001, p = 0.002 and p = 0.0005, respectively). Moreover, selenium levels presented lower mean values in cancer patients relative to control groups (SMD = −0.39 µg/L; 95% CI: −0.64, −0.14; p = 0.002, I2 = 85%). Conclusion: GPX4 (rs713041) T allele may influence colorectal cancer risk, stroke, hypertension and pre-eclampsia. In addition, low selenium levels may play a role in the increased risk of cancer.
Topics: Female; Humans; Pregnancy; Colorectal Neoplasms; Genetic Predisposition to Disease; Glutathione Peroxidase; Hypertension; Phospholipid Hydroperoxide Glutathione Peroxidase; Polymorphism, Single Nucleotide; Pre-Eclampsia; Selenium; Stroke
PubMed: 36555402
DOI: 10.3390/ijms232415762 -
Pharmaceuticals (Basel, Switzerland) May 2020Epilepsy is a serious neurological disorder affecting around 70 million people globally and is characterized by spontaneous recurrent seizures. Recent evidence indicates... (Review)
Review
Epilepsy is a serious neurological disorder affecting around 70 million people globally and is characterized by spontaneous recurrent seizures. Recent evidence indicates that dysfunction in metabolic processes can lead to the alteration of neuronal and network excitability, thereby contributing to epileptogenesis. Developing a suitable animal model that can recapitulate all the clinical phenotypes of human metabolic epilepsy (ME) is crucial yet challenging. The specific environment of many symptoms as well as the primary state of the applicable neurobiology, genetics, and lack of valid biomarkers/diagnostic tests are the key factors that hinder the process of developing a suitable animal model. The present systematic review summarizes the current state of available animal models of metabolic dysfunction associated with epileptic disorders. A systematic search was performed by using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) model. A range of electronic databases, including google scholar, Springer, PubMed, ScienceDirect, and Scopus, were scanned between January 2000 and April 2020. Based on the selection criteria, 23 eligible articles were chosen and are discussed in the current review. Critical analysis of the selected literature delineated several available approaches that have been modeled into metabolic epilepsy and pointed out several drawbacks associated with the currently available models. The result describes available models of metabolic dysfunction associated with epileptic disorder, such as mitochondrial respiration deficits, Lafora disease (LD) model-altered glycogen metabolism, causing epilepsy, glucose transporter 1 (GLUT1) deficiency, adiponectin responsive seizures, phospholipid dysfunction, glutaric aciduria, mitochondrial disorders, pyruvate dehydrogenase (PDH) α-subunit gene (PDHA1), pyridoxine dependent epilepsy (PDE), BCL2-associated agonist of cell death (BAD), Kcna1 knock out (KO), and long noncoding RNAs (lncRNA) cancer susceptibility candidate 2 (lncRNA CASC2). Finally, the review highlights certain focus areas that may increase the possibilities of developing more suitable animal models and underscores the importance of the rationalization of animal models and evaluation methods for studying ME. The review also suggests the pressing need of developing precise robust animal models and evaluation methods for investigating ME.
PubMed: 32466498
DOI: 10.3390/ph13060106 -
Advances in Nutrition (Bethesda, Md.) Dec 2022Reported breast milk lipid concentrations may vary with geographical region, postnatal age, and year of sample collection. In this review, we summarized data on the... (Meta-Analysis)
Meta-Analysis
Reported breast milk lipid concentrations may vary with geographical region, postnatal age, and year of sample collection. In this review, we summarized data on the concentrations of total fat, total phospholipids, cholesterol, and fatty acids in human milk worldwide and their variation according to lactation stage, study area, and sample collection year. A systematic literature search was performed using the PubMed, Embase, Web of Science, and Medline databases for English-language papers and Wanfang and China National Knowledge Infrastructure databases for Chinese-language papers. A total of 186 studies evaluating the human milk lipid profiles were included. According to random-effects models based on worldwide data, the summarized means (95% CIs) as percentages of total fat were 42.2% (41.1%, 43.3%) for SFAs, 36.6% (35.6%, 37.5%) for MUFAs, and 21.0% (19.3%, 22.7%) for PUFAs. However, the study heterogeneity was high for most types of fatty acids (I2 > 99%). Human milk from Western countries had higher concentrations of MUFAs and 18:1n-9 (ω-9), but lower concentrations of PUFAs, 18:2n-6, 20:4n-6, 18:3n-3, 20:5n-3, 22:6n-3, and total n-6 PUFA compared with those from non-Western countries (P < 0.001-0.011). Significant lactation stage differences were observed for total fat and some individual fatty acids. The concentrations of SFAs and 16:0 were significantly negatively correlated with sampling year (P < 0.001-0.028). In contrast, a significant positive correlation between the concentrations of 18:2n-6 and 18:3n-3 and sampling year was observed (P < 0.001-0.035). Our results suggest that the pooling of data on human milk lipid profiles in different studies should be done with caution due to the high between-study heterogeneity. The concentration of lipids, including total fat, cholesterol, and specific fatty acids, differs in human milk according to lactation stage, geographical region, and year of sample collection.
Topics: Female; Humans; Milk, Human; Fatty Acids; Fatty Acids, Unsaturated; Lactation; Breast Feeding
PubMed: 36083999
DOI: 10.1093/advances/nmac097