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Frontiers in Endocrinology 2023In this comprehensive review, we examine the main preclinical and clinical investigations assessing the effects of different forms of choline supplementation currently... (Review)
Review
In this comprehensive review, we examine the main preclinical and clinical investigations assessing the effects of different forms of choline supplementation currently available, including choline alfoscerate (CHNOP), also known as alpha-glycerophosphocholine (α-GPC, or GPC), choline bitartrate, lecithin, and citicoline, which are cholinergic compounds and precursors of acetylcholine. Extensively used as food supplements, they have been shown to represent an effective strategy for boosting memory and enhancing cognitive function.
Topics: Choline; Glycerylphosphorylcholine; Acetylcholine; Dietary Supplements; Cytidine Diphosphate Choline
PubMed: 36950691
DOI: 10.3389/fendo.2023.1148166 -
International Journal of Molecular... Dec 2021-alpha glycerylphosphorylcholine (GPC), a nutritional supplement, has been demonstrated to improve neurological function. However, a new study suggests that GPC...
-alpha glycerylphosphorylcholine (GPC), a nutritional supplement, has been demonstrated to improve neurological function. However, a new study suggests that GPC supplementation increases incident stroke risk thus its potential adverse effects warrant further investigation. Here we show that GPC promotes atherosclerosis in hyperlipidemic mice. GPC can be metabolized to trimethylamine N-oxide, a pro-atherogenic agent, suggesting a potential molecular mechanism underlying the observed atherosclerosis progression. GPC supplementation shifted the gut microbial community structure, characterized by increased abundance of , , and and decreased abundance of , , and , as determined by 16S rRNA gene sequencing. These data are consistent with a reduction in fecal and cecal short chain fatty acids in GPC-fed mice. Additionally, we found that GPC supplementation led to an increased relative abundance of choline trimethylamine lyase ()-encoding bacteria via qPCR. Interrogation of host inflammatory signaling showed that GPC supplementation increased expression of the proinflammatory effectors CXCL13 and TIMP-1 and activated NF-κB and MAPK signaling pathways in human coronary artery endothelial cells. Finally, targeted and untargeted metabolomic analysis of murine plasma revealed additional metabolites associated with GPC supplementation and atherosclerosis. In summary, our results show GPC promotes atherosclerosis through multiple mechanisms and that caution should be applied when using GPC as a nutritional supplement.
Topics: Animals; Apolipoproteins E; Atherosclerosis; Cecum; Cell Line; Dietary Supplements; Endothelial Cells; Fatty Acids, Volatile; Feces; Female; Gastrointestinal Microbiome; Glycerylphosphorylcholine; Humans; Male; Methylamines; Mice; Mice, Inbred C57BL; RNA, Ribosomal, 16S
PubMed: 34948275
DOI: 10.3390/ijms222413477 -
JAMA Network Open Nov 2021L-α glycerylphosphorylcholine (α-GPC, choline alphoscerate) is used globally by individuals older than 50 years based on its potential function as a precursor of...
IMPORTANCE
L-α glycerylphosphorylcholine (α-GPC, choline alphoscerate) is used globally by individuals older than 50 years based on its potential function as a precursor of acetylcholine. However, choline has previously been linked to a higher risk of cardiovascular disease via trimethylamine-N-oxide, a metabolite of choline by microbiota.
OBJECTIVE
To investigate the association between α-GPC use and subsequent 10-year stroke risk.
DESIGN, SETTING, AND PARTICIPANTS
A population-based, retrospective cohort study was conducted using data from the National Health Insurance Service of South Korea. Participants included men and women aged 50 years or older without underlying stroke or Alzheimer disease (N = 12 008 977).
MAIN OUTCOMES AND MEASURES
All participants were divided into whether they were prescribed α-GPC during 2006-2008. α-GPC users were matched with nonusers for all covariates to create a matched cohort. α-GPC use was further divided into durations less than 2, 2 to 6, 6 to 12, and more than 12 months of α-GPC prescriptions. The adjusted hazard ratios (aHRs) and 95% CIs for total stroke, ischemic stroke, and hemorrhagic stroke from January 1, 2009, to January 31, 2018, were calculated by multivariate Cox proportional hazards regression.
RESULTS
A total of 12 008 977 individuals (6 401 965 [53.3%] women) aged 50 years or older were included in the study. The mean (SD) age was 61.6 (9.4) years for nonusers and 68.3 (10.0) years for users, and that of the matching cohort was 68.2 (9.9) years for both groups. Compared with α-GPC nonusers (n = 11 900 100), users (n = 108 877) had a higher risk for total stroke (aHR, 1.46; 95% CI, 1.43-1.48), ischemic stroke (aHR 1.36; 95% CI, 1.33-1.39), and hemorrhagic stroke (aHR, 1.36; 95% CI, 1.28-1.44). After matching for all covariates, α-GPC users had a higher risk for total stroke (aHR, 1.43; 95% CI, 1.41-1.46), ischemic stroke (aHR, 1.34; 95% CI, 1.31-1.37), and hemorrhagic stroke (aHR, 1.37; 95% CI, 1.29-1.46). Increasing intake of α-GPC was associated with a higher risk for total stroke in a dose-response manner.
CONCLUSIONS AND RELEVANCE
In this cohort study, use of α-GPC was associated with a higher 10-year incident stroke risk in a dose-response manner after adjusting for traditional cerebrovascular risk factors. Future studies are needed to determine the possible mechanisms behind the potential cerebrovascular risk-elevating effects of α-GPC.
Topics: Aged; Aged, 80 and over; Alzheimer Disease; Biological Monitoring; Cohort Studies; Female; Glycerylphosphorylcholine; Humans; Male; Middle Aged; Proportional Hazards Models; Republic of Korea; Retrospective Studies; Risk Assessment; Risk Factors; Stroke
PubMed: 34817582
DOI: 10.1001/jamanetworkopen.2021.36008 -
International Journal of Molecular... Apr 2021Choline is essential for maintaining the structure and function of cells in humans. Choline plays an important role in eye health and disease. It is a precursor of... (Review)
Review
Choline is essential for maintaining the structure and function of cells in humans. Choline plays an important role in eye health and disease. It is a precursor of acetylcholine, a neurotransmitter of the parasympathetic nervous system, and it is involved in the production and secretion of tears by the lacrimal glands. It also contributes to the stability of the cells and tears on the ocular surface and is involved in retinal development and differentiation. Choline deficiency is associated with retinal hemorrhage, glaucoma, and dry eye syndrome. Choline supplementation may be effective for treating these diseases.
Topics: Acetylcholine; Animals; Choline; Choline Deficiency; Diabetic Retinopathy; Dry Eye Syndromes; Eye Diseases; Eye Pain; Glaucoma; Glycerylphosphorylcholine; Humans; Lacrimal Apparatus; Lens, Crystalline; Nociception; Optic Nerve; Parasympathetic Nervous System; Phosphatidylcholines; Phospholipids; Receptors, Nicotinic; Retina; Retinal Vessels; Tears
PubMed: 33946979
DOI: 10.3390/ijms22094733 -
Journal of Ophthalmology 2022Cataract surgery is widespread. The surgical procedure is associated with damage to the epithelial barrier and interruption of the corneal innervation. In addition,...
Cataract surgery is widespread. The surgical procedure is associated with damage to the epithelial barrier and interruption of the corneal innervation. In addition, pathological events sustain signs and symptoms that may persist for a long time. Recently, a fixed combination of alpha-glycerylphosphorylcholine and D-Panthenol (Oftassiale) has been available as eye drops. The present study investigated the effects of an Oftassiale therapy in 20 patients undergoing cataract surgery. A comparison group included 20 patients treated with topical hyaluronic acid. Standard prophylactic and anti-inflammatory treatment was prescribed to all patients. Clinical signs and symptoms were assessed over time. In vivo confocal microscopy (IVCM) was performed accordingly. Oftassiale treatment significantly reduced clinical features and improved IVCM outcomes. In addition, therapy was well-tolerated, and no clinically significant adverse events occurred. In conclusion, this study confirmed that IVCM helps assess the tunnel after cataract surgery due to its ability to provide microscopic details in vivo. Topical therapy with alpha-glycerylphosphorylcholine and D-Panthenol eye drops promoted and stabilized the reepithelialization process. This fixed combination also accelerated and modulated the repair of the corneal innervation. Moreover, this treatment was well-tolerated and safe.
PubMed: 35711284
DOI: 10.1155/2022/1951014 -
ACS Omega Jun 2020The liquified mash of milled grains from the Canadian wheat cultivar, AC Andrew, was fermented to determine whether α-glycerylphosphorylcholine (α-GPC) accumulated and...
The liquified mash of milled grains from the Canadian wheat cultivar, AC Andrew, was fermented to determine whether α-glycerylphosphorylcholine (α-GPC) accumulated and whether the accumulation was dependent on fermentation-related factors. Fermentation was conducted at a temperature of 37 °C for 7 days (168 h) with samples collected every 24 h. The samples were analyzed using a proton nuclear magnetic resonance water suppression pulse sequence to allow the quantitation of ethanol, acetic acid, lactic acid, succinic acid, glycerol, phenethyl alcohol, betaine, and α-GPC. A Gompertz model was used to interpret fermentation kinetics for each analyte, and during fermentation, ethanol accumulated to a concentration of 72.1 g/L while α-GPC accumulated to a concentration of 1.68 g/L over 72 h. There were significant and positive correlations between the accumulation of α-GPC, ethanol, lactic acid, and glycerol and acetic acid production. Furthermore, there were no significant negative correlations between the productions of these compounds; hence, all the compounds accumulated during fermentation were produced simultaneously with no observed decrease measured in any compound. This indicates that α-GPC can be successfully produced industrially without any negative impact on ethanol or other useful compounds.
PubMed: 32548433
DOI: 10.1021/acsomega.0c01352 -
Reproduction, Fertility, and Development Oct 2014Basal cells are present in the columnar pseudostratified epithelium covering the epididymis of all mammalian species, which regulates the microenvironment where the... (Review)
Review
Basal cells are present in the columnar pseudostratified epithelium covering the epididymis of all mammalian species, which regulates the microenvironment where the functionally incompetent germ cells produced by the testis are matured and stored. Striking novelties have come from investigations on epididymal basal cells in the past 30-40 years. In addition to an earlier hypothesised scavenger role for basal cells, linked to their proven extratubular origin and the expression of macrophage antigens, basal cells have been shown to be involved in cell-cell cross-talk, as well as functioning as luminal sensors to regulate the activity of principal and clear cells. Involvement of basal cells in the regulation of electrolyte and water transport by principal cells was hypothesised. This control is suggested to be mediated by the local formation of prostaglandins. Members of the aquaporin (AQP) and/or aquaglyceroporin family (AQP3, AQP7 and AQP8) are also specifically expressed in the rat epididymal basal cells. Transport of glycerol and glycerylphosphorylcholine from the epithelium of the epididymis to the lumen in relation to sperm maturation may be mediated by AQP. Most probably basal cells collaborate to the building up of the blood-epididymis barrier through cell adhesion molecules, implying an involvement in immune control exerted towards sperm cells, which are foreigners in the environment in which they were produced.
Topics: Animals; Aquaporins; Cell Communication; Cell Differentiation; Cell Lineage; Epididymis; Epithelial Cells; Glycerol; Glycerylphosphorylcholine; Male; Prostaglandins; Signal Transduction; Spermatozoa
PubMed: 24138802
DOI: 10.1071/RD13301 -
Cell Death & Disease Oct 2022The short-chain dehydrogenase/reductase (SDR) superfamily has essential roles in lipid metabolism and redox sensing. In recent years, accumulating evidence highlights...
The short-chain dehydrogenase/reductase (SDR) superfamily has essential roles in lipid metabolism and redox sensing. In recent years, accumulating evidence highlights the emerging association between SDR family enzymes and cancer. Dehydrogenase/reductase member 2(DHRS2) belongs to the NADH/NADPH-dependent SDR family, and extensively participates in the regulation of the proliferation, migration, and chemoresistance of cancer cells. However, the underlying mechanism has not been well defined. In the present study, we have demonstrated that DHRS2 inhibits the growth and metastasis of ovarian cancer (OC) cells in vitro and in vivo. Mechanistically, the combination of transcriptome and metabolome reveals an interruption of choline metabolism by DHRS2. DHRS2 post-transcriptionally downregulates choline kinase α (CHKα) to inhibit AKT signaling activation and reduce phosphorylcholine (PC)/glycerophosphorylcholine (GPC) ratio, impeding choline metabolism reprogramming in OC. These actions mainly account for the tumor-suppressive role of DHRS2 in OC. Overall, our findings establish the mechanistic connection among metabolic enzymes, metabolites, and the malignant phenotype of cancer cells. This could result in further development of novel pharmacological tools against OC by the induction of DHRS2 to disrupt the choline metabolic pathway.
Topics: Carbonyl Reductase (NADPH); Carcinoma, Ovarian Epithelial; Cell Line, Tumor; Cell Proliferation; Choline; Choline Kinase; Down-Regulation; Female; Glycerylphosphorylcholine; Humans; NAD; NADP; Ovarian Neoplasms; Oxidoreductases; Phosphorylcholine; Proto-Oncogene Proteins c-akt
PubMed: 36192391
DOI: 10.1038/s41419-022-05291-w -
Journal of the International Society of... Dec 2023Nutrition plays a key role in training and athletic performance and dietary supplements can make a small, but potentially valuable, contribution to achieving peak... (Randomized Controlled Trial)
Randomized Controlled Trial
Effects of branched chain amino acids, l-citrulline, and alpha-glycerylphosphorylcholine supplementation on exercise performance in trained cyclists: a randomized crossover trial.
BACKGROUND
Nutrition plays a key role in training and athletic performance and dietary supplements can make a small, but potentially valuable, contribution to achieving peak athletic performance. This study is the first to investigate the effects of supplementation from the combination of BCAAs, L-citrulline, and A-GPC on exercise performance.
METHODS
In this randomized, double-blind, crossover study 30 male trained cyclists (age: 43.7 ± 8.5 years) completed a 20 km cycling time trial (TT) test and a high intensity endurance cycling (HIEC) test following a 7-day supplementation period with either a supplement containing 8 g BCAAs, 6 g L-citrulline, and 300 mg A-GPC or a placebo (15 g maltodextrin). For each trial, mean values for time to completion, peak and average power output, OMNI rating of perceived exertion, and visual analogue scale (VAS) responses on perceived exertion were computed for the 20 km TT test. Mean values for time to fatigue and VAS responses on perceived exertion were computed for the HIEC test. Procedures for dietary intake and exercise patterns were implemented to achieve consistency throughout the study period.
RESULTS
There was a significant increase ( = .003) in peak power in the 20 km TT (354.27 ± 87.88 and 321.67 ± 63.65, for supplement and placebo trials, respectively) and a significant increase ( = .001) in time to fatigue in the HIEC test (0:19:49 ± 0:11:13 min and 0:14:33 ± 0:09:59 min, for supplement and placebo trials, respectively) with the test supplement compared to the placebo. With the test supplement, there was an average increase in TT peak power of 11% and an average increase in time to fatigue of 36.2% in the HIEC test compared to the placebo. There was no significant improvement in time to completion, average power, OMNI rating of perceived exertion, or VAS responses on perceived exertion in the TT test and no significant improvement in VAS measures of perceived exertion in the HIEC test.
CONCLUSIONS
The combination of BCAAs, L-citrulline, and A-GPC used in this study improves cycling performance and may be useful for individuals seeking to improve athletic performance, particularly in disciplines requiring lower body muscular strength and endurance.
Topics: Humans; Male; Adult; Middle Aged; Cross-Over Studies; Citrulline; Glycerylphosphorylcholine; Amino Acids, Branched-Chain; Athletic Performance; Dietary Supplements; Fatigue; Double-Blind Method; Bicycling
PubMed: 37229544
DOI: 10.1080/15502783.2023.2214112 -
Nutrients Sep 2022The current study examined the effects of Alpha-Glycerylphosphorylcholine (A-GPC) on heart rate variability (HRV) and hemodynamic responses following a sprint interval... (Randomized Controlled Trial)
Randomized Controlled Trial
The current study examined the effects of Alpha-Glycerylphosphorylcholine (A-GPC) on heart rate variability (HRV) and hemodynamic responses following a sprint interval exercise (SIE) in women who were overweight or obese. Participants (n = 12, 31.0 ± 4.6 years; 29.4 ± 2.1 kg/m2) consumed 1000 mg of A-GPC or a placebo after eating breakfast in a randomized, double-blind cross-over design. After 60 min, participants performed two bouts of the SIE (30 s Wingate) interspersed with 4 min of active recovery (40 rpm). Hemodynamic variables and HRV domains were measured before and 60 min after the A-GPC consumption, immediately after SIE, and every 15 min up to 120 min during recovery. A-GPC consumption increased resting levels of both the time domain (Standard Deviation of RR wave intervals [SDNN] and percentage of interval differences of adjacent RR intervals greater than 50 ms [pNN50%]) and frequency domain (high frequency [HF] and low frequency [LF]) variables of HRV (p < 0.05). Moreover, HRV variables (except for LF/HF) decreased (p < 0.05) immediately after SIE in the A-GPC and placebo sessions. Systolic and diastolic blood pressure increased (p < 0.05) immediately after SIE in both trials. Both HRV and hemodynamic variables recovered (p < 0.05) faster in the A-GPC compared to the placebo session. We concluded that A-GPC consumption recovers HRV and blood pressure faster following strenuous exercise in overweight and obese women, and that it might favorably modify cardiac autonomic function.
Topics: Autonomic Nervous System; Female; Glycerylphosphorylcholine; Heart Rate; Humans; Obesity; Overweight
PubMed: 36235623
DOI: 10.3390/nu14193970